Clinical trial NCT04677179
Conditions: Colitis, Ulcerative
Keywords: T regulatory cells (Tregs) Interleukin 2 Interleukin-2
Sponsor: Nektar Therapeutics
Start date: 2021-03-22; Completion date: 2022-08-09
Enrollment: 81 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The reason for this study is to determine if the study drug LY3471851 is safe and effective in adult participants with active ulcerative colitis (UC). The study treatment will last about 52 weeks.

Detailed description:
In stage 1, two doses (high and low) of LY3471851 will be compared to placebo. In stage 2, up to two additional doses (to be confirmed) of LY3471851 will be compared to placebo.

LY3471851 (NKTR-358) is a potential first-in-class therapeutic that may address an underlying immune system imbalance in people with many autoimmune conditions. It targets the interleukin (IL-2) receptor complex in the body in order to stimulate proliferation of inhibitory immune cells known as regulatory T cells. By activating these cells, LY3471851 may act to bring the immune system back into balance.

Arms: arm 1: Participants received a subcutaneous injection of high dose LY3471851 every 2 weeks from weeks 0 to 12. Week 12 responders entered the maintenance period and continued with the same treatment. Week 12 non-responders entered the extension period where they received subcutaneous injection of high dose LY3471851 every 2 weeks up to week 50. At week 26, extension period non-responders were discontinued from treatment. Post-treatment, participants entered follow-up period and were observed for 6 weeks for safety. arm 2: Participants received a subcutaneous injection of low dose LY3471851 every 2 weeks from weeks 0 to 12. Week 12 responders entered the maintenance period and continued with the same treatment. Week 12 non-responders entered the extension period where they received subcutaneous injection of high dose LY3471851 every 2 weeks up to week 50. At week 26, extension period non-responders were discontinued from treatment. Post-treatment, participants entered follow-up period and were observed for 6 weeks for safety. arm 3: Participants received a subcutaneous injection of placebo every 2 weeks from weeks 0 to 12. Week 12 responders entered the maintenance period and continued with the same treatment. Week 12 non-responders entered the extension period where they received subcutaneous injection of high dose LY3471851 every 2 weeks up to week 50. At week 26, extension period non-responders were discontinued from treatment. Post-treatment, participants entered follow-up period and were observed for 6 weeks for safety.
Interventions: intervention 1: LY3471851 intervention 2: Placebo
Intervention descriptions: intervention 1: administered SC intervention 2: administered SC

Protocol documents:
Prot_000.pdf: 
 
 
 
Protocol J1P-MC-KFAH(b) 
 
An AdapƟve Phase 2, Randomized, Double-Blind, 
Placebo-Controlled Study of LY3471851 (NKTR-
358) in PaƟents with Moderately to Severely 
AcƟve UlceraƟve ColiƟs 
 
NCT04677179 
 
Approval Date: 03-Jun-2021 


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
1
Title P a ge
C o nfi d e nti al i nf or m ati o n
T h e i nf or m ati o n c o nt ai n e d i n t hi s d o c u m e nt i s c o nfi d e nti al a n d i s i nt e n d e d f or t h e u s e of cli ni c al i n v e sti g at or s. It i s t h e p r o p ert y of 
Eli Lill y a n d C o m p a n y or it s s u b si di ari e s a n d s h o ul d n ot b e c o pi e d b y or di stri b ut e d t o p er s o n s n ot i n v ol v e d i n t h e cli n i c al 
i n v e sti g ati o n of N K T R -3 5 8 (L Y 3 4 7 1 8 5 1 ), u nl e s s s u c h p er s o n s ar e b o u n d b y a c o nfi d e nti alit y a gr e e m e nt wit h Eli Lill y a n d 
C o m p a n y or it s s u b si di ari e s.
N ot e t o R e g ul at or y A ut h oriti e s : T hi s d o c u m e nt m a y c o nt ai n pr ot e ct e d p er s o n al d at a a n d/ or c o m m er ci all y co nfi d e nti al 
i nfor m ati o n e x e m pt fr o m p u bli c di s cl o s ur e. Eli Lill y a n d C o m p a n y r e q u e st s c o n s ult ati o n r e g ar di n g r el e a s e/r e d a cti o n pri or t o a n y 
p u bli c r el e a s e. I n t h e U nit e d St at e s, t hi s d o c u m e nt i s s u bj e ct t o Fr e e d o m of I nf or m ati o n A ct ( F OI A) E x e m pti o n 4 a n d m a y n ot b e 
r epr o d u c e d or ot h er wi s e di s s e mi n at e d wit h o ut t h e writt e n a p pr o v al of Eli Lill y a n d C o m p a n y or it s s u b si di ari e s.
Pr ot oc ol Title: A n A da pt i ve P hase 2, Ra n d omize d, D o u ble -Bli n d, Pl ace b o -C o ntr olle d St u d y  of 
L Y 3 4 7 1 8 5 1 ( N K T R -3 5 8) i n Pati e nts wit h M o deratel y t o Se verel y Acti ve Ulcerat i ve C olitis
Pr ot oc ol N u m ber: J 1 P-M C -K F A H
A me n d me nt N u m ber: b
C o m p o u n d: L Y 3 4 7 1 8 5 1
St u d y P h ase: 2
Acr o n y m: I N S T R U C T-U C
S p o ns or N a me: El i Lill y  a n d C o mpa n y
Le g al Re gistere d A d dress:
I n dia na p olis, I n dia na, U S A 4 6 2 8 5
Re g ul at or y A ge nc y I de ntifier N u m bers :
I N D: 1 5 1 2 1 6
E u dra C T : 2 0 2 0- 0 0 3 0 1 7- 3 5
A p pr o v al D ate : Pr ot oc ol A me n d me nt ( b) Electr o nicall y Si g ne d a n d A p pr o ve d b y Lill y o n date 
pr o vi de d bel o w .
A p pr o v al D at e: 0 3- J u n- 2 0 2 1 G M T


CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
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The medical monitor name and contact information will be provided separately.


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Protocol J1P-MC-KFAH(b)
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Protocol Amendment Summary of Changes Table
DOCUMENT HISTORY
Document
Date
Amendment (a)
18 November 2020
Original Protocol
03 September 2020
Amendment b
This amendment is considered to be non-substantial based on the criteria set forth in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the European 
Union.
Overall Rationale for the Amendment:
The main purpose of this protocol amendment is to modify the study entry criteria and dose 
preparation for site clarification. 
Section Number and Name
Description of Change
Brief Rationale
5.1. Inclusion Criteria
Added Note to clarify Inclusion 
Criterion 6 
For site clarification
5.4.2 Rescreening of 
Individuals Who Fail 
Screening
Updated table to reflect Exclusion 
Criterion 42
For site clarification
6.1 Study Interventions 
Administered
Dose Preparation
For site clarification


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Protocol J1P-MC-KFAH(b)
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Table of Contents
Title Page ................................................................................................................................................ 1
Table of Contents .................................................................................................................................... 4
1. Protocol Summary............................................................................................................................... 9
1.1. Synopsis........................................................................................................................................9
1.2. Schema.......................................................................................................................................13
1.3. Schedule of Activities (SoA).........................................................................................................16
1.3.1. Schedule of Activities for the Screening and Induction Treatment Periods............................ 16
1.3.2. Schedule of Activities for the Maintenance Treatment Period.............................................. 23
1.3.3. Schedule of Activities for the Extension Induction and Extension Maintenance Periods........ 32
1.3.4. Schedule of activities for ETV, unscheduled visits, and Post-Treatment Follow-Up Period..... 42
2. Introduction ...................................................................................................................................... 46
2.1. Study Rationale........................................................................................................................... 46
2.2. Background.................................................................................................................................46
2.3. Benefit/Risk Assessment.............................................................................................................47
3. Objectives and Endpoints .................................................................................................................. 49
4. Study Design...................................................................................................................................... 52
4.1. Overall Design............................................................................................................................. 52
4.2. Scientific Rationale for Study Design ........................................................................................... 54
4.2.1. Participant Input into Design................................................................................................ 55
4.3. Justification for Dose...................................................................................................................55
4.4. End of Study Definition ...............................................................................................................56
5. Study Population ............................................................................................................................... 57
5.1. Inclusion Criteria......................................................................................................................... 57
5.2. Exclusion Criteria ........................................................................................................................ 61
5.3. Lifestyle Considerations ..............................................................................................................66
5.4. Screen Failures............................................................................................................................ 66
5.4.1. Allowed Retesting of Screening Investigations...................................................................... 66
5.4.2. Rescreening of Individuals Who Fail Screening ..................................................................... 67
6. Study Intervention............................................................................................................................. 69
6.1. Study Interventions Administered............................................................................................... 69
6.2. Preparation/Handling/Storage/Accountability ............................................................................70
6.3. Measures to Minimize Bias: Randomization and Blinding............................................................ 71


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Protocol J1P-MC-KFAH(b)
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6.4. Study Intervention Compliance...................................................................................................72
6.5. Concomitant Therapy..................................................................................................................72
6.6. Dose Modification....................................................................................................................... 74
6.7. Intervention after the End of the Study....................................................................................... 74
7. Discontinuation of Study Intervention and Participant Discontinuation/Withdrawal.......................... 75
7.1. Discontinuation of Study Intervention......................................................................................... 75
7.1.1. Criteria for Permanent Discontinuation of Study Drug.......................................................... 75
7.1.2. Criteria for Temporary Interruption (Withholding) of Study Drug ......................................... 78
7.1.2.1. Infection-Related Criteria for Temporary Interruption of Study Drug ............................. 78
7.1.2.2. Other Criteria for Temporary Interruption of Study Drug............................................... 79
7.2. Participant Discontinuation/Withdrawal from the Study ............................................................. 79
7.2.1. Discontinuation of Inadvertently Enrolled Participants......................................................... 80
7.3. Lost to Follow up......................................................................................................................... 80
8. Study Assessments and Procedures ................................................................................................... 81
8.1. Efficacy Assessments...................................................................................................................81
8.1.1. Primary Efficacy Assessment................................................................................................ 82
8.1.1.1. Primary Endpoint........................................................................................................... 82
8.1.1.2. Mayo Score ................................................................................................................... 82
8.1.1.3. Endoscopy..................................................................................................................... 83
8.1.2. Secondary Efficacy Assessments........................................................................................... 85
8.1.2.1. Endoscopic Biopsies ...................................................................................................... 85
8.1.2.2. Geboes Score ................................................................................................................ 85
8.1.2.3. Patient-Reported Outcome Instruments........................................................................ 85
8.1.3. Exploratory Efficacy Assessments......................................................................................... 86
8.2. Safety Assessments.....................................................................................................................86
8.2.1. Vital Signs ............................................................................................................................ 87
8.2.2. Physical Examinations .......................................................................................................... 88
8.2.3. Electrocardiograms .............................................................................................................. 89
8.2.4. Chest Radiography............................................................................................................... 89
8.2.5. Laboratory Tests .................................................................................................................. 89
8.2.5.1. Pregnancy Testing ......................................................................................................... 90
8.2.6.Tuberculosis Testing and Monitoring..................................................................................... 91
8.2.7. Hepatitis B Testing and Monitoring ...................................................................................... 92


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Pr ot oc ol  J 1 P-M C -K F A H( b)
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8. 2. 8. H e p atitis C T esti n g a n d M o nit ori n g ...................................................................................... 9 3
8. 2. 9. H e p atic S af et y M o nit ori n g ................................................................................................... 9 3
8. 2. 9. 1. A d diti o n al H e p atic D at a C oll ecti o n i n P artici p a nts W h o H a v e A b n or m al Li v er T ests D uri n g 
t h e St u dy ................................................................................................................................... 9 5
8. 2. 1 0. S uici d al I d e ati o n a n d B e h a vi or Ris k M o nit ori n g .................................................................. 9 5
8. 2. 1 0. 1. C ol u m bi a S uici d e -S e v erit y R ati n g Sc al e ........................................................................ 9 5
8. 2. 1 0. 2. D e pr essi o n Ass ess m e nt wit h 1 6 -It e m Q uic k I n v e nt or y of D e pr essi v e S y m pt o m at ol o g y–
S elf R e p ort .................................................................................................................................9 6
8. 3. A d v ers e Ev e nts a n d S eri o us A dv ers e Ev e nts ................................................................................9 6
8. 3. 1. Ti m e P eri o d a n d Fr e q u e nc y f or C oll ecti n g A dv ers e Ev e nt a n d S eri o us A dv ers e Ev e nt 
I nf or mati o n ................................................................................................................................... 9 7
8. 3. 1. 1. A d v ers e E v e nt M o nit ori n g wit h a S yst e m atic Q u esti o n n air e .......................................... 9 7
8. 3. 2. M et h o d of D et ecti n g A dv ers e Ev e nts a n d S eri o us A dv ers e Ev e nts ........................................ 9 7
8. 3. 3. F oll o w -u p of A dv ers e Ev e nts a n d S eri o us A dv ers e Ev e nts ..................................................... 9 8
8. 3. 4. R e g ul at or y R e p orti n g R e q u ir e m e nts f or S eri o us A d v ers e E v e nts .......................................... 9 8
8. 3. 5. Pr e g n a nc y ............................................................................................................................ 9 8
8. 3. 6. A d v ers e E v e nts of S p eci al I nt er est ........................................................................................ 9 8
8. 3. 6. 1. S yst e mic H y p ers e nsiti vit y R e acti o ns .............................................................................. 9 9
8. 3. 6. 2. S eri o us I nf ecti o ns a n d O p p ort u nistic I nf ecti o ns ............................................................. 9 9
8. 3. 6. 3. I nj ecti o n Sit e Ass ess m e nt .............................................................................................. 9 9
8. 3. 7. C o m pl ai nt H a n dli n g .............................................................................................................. 9 9
8. 4. Tr e at m e nt of Ov er d os e .............................................................................................................1 0 0
8. 5. P h ar m ac o ki n etics ......................................................................................................................1 0 0
8. 6. P h ar m ac o d y n a mics ...................................................................................................................1 0 1
8. 7. G e n etics ....................................................................................................................................1 0 1
8. 8. Bi o m ar k ers ...............................................................................................................................1 0 2
8. 9. 
...................................................................................................1 0 3
8. 1 0. M e dic al R es o urc e Utiliz ati o n a n d H e alt h Ec o n o mics ................................................................1 0 3
9. St atistic al C o nsi d er ati o ns ................................................................................................................. 1 0 4
9. 1. St atistic al H y p ot h es es ...............................................................................................................1 0 4
9. 2. S a m pl e Siz e D et er mi n ati o n .......................................................................................................1 0 4
9. 3. P o p ul ati o ns f or A n al ys es ...........................................................................................................1 0 5
9. 4. St atistic al A n al ys es ....................................................................................................................1 0 5
9. 4. 1. G e n er al C o nsi d er ati o ns ...................................................................................................... 1 0 5
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Pr ot oc ol  J 1 P-M C -K F A H( b)
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9. 4. 1. 1. Est i m a n ds.................................................................................................................... 1 0 7
9. 4. 1. 2. Missi n g D at a I m p ut ati o n ............................................................................................. 1 0 7
9. 4. 1. 3. A dj ust m e nt f or M ulti pl e C o m p aris o ns ......................................................................... 1 0 8
9. 4. 2. Tr e at m e nt Gr o u p C o m p ar a bilit y ......................................................................................... 1 0 8
9. 4. 2. 1. P artici p a nt Dis p ositi o n .................................................................................................1 0 8
9. 4. 2. 2. P artici p a nt C h ar act eristics ........................................................................................... 1 0 8
9. 4. 2. 3. C o nc o mit a nt T h er a p y .................................................................................................. 1 0 8
9. 4. 2. 4. Tr e at m e nt C o m pli a nc e ................................................................................................ 1 0 9
9. 4. 3. Effic ac y A n al ys es ................................................................................................................ 1 0 9
9. 4. 3. 1. Pri m ar y A n al ys es ......................................................................................................... 1 0 9
9. 4. 3. 2. S ec o n d ar y A n al ys es ..................................................................................................... 1 0 9
9. 4. 4. S af et y A n al ys es .................................................................................................................. 1 0 9
9. 4. 5. P h ar m ac o ki n etic/ P h ar m ac o d y n a mic A n al ys es .................................................................... 1 1 0
9. 4. 6. 
............................................................................................ 1 1 0
9. 4. 7. S u b gr o u p, S u p pl e m e nt al, a n d Ot h er Ex pl or at or y A n al ys es ................................................. 1 1 1
9. 5. I nt eri m A n al ys es .......................................................................................................................1 1 1
9. 6. D at a M o nit ori n g C o m mitt e e .....................................................................................................1 1 2
1 0. S u p p orti n g D oc u m e nt ati o n a n d O p er ati o n al C o nsi d er ati o ns .......................................................... 1 1 3
1 0. 1. A p p e n dix 1: R e g ul at or y, Et hic al, a n d St u d y O v ersi g ht C o nsi d er ati o ns ......................................1 1 3
1 0. 1. 1. R e g ul at or y a n d Et hic al C o nsi d er ati o ns .............................................................................. 1 1 3
1 0. 1. 2. Fi n a nci al Discl os ur e .......................................................................................................... 1 1 3
1 0. 1. 3. I nf or m e d C o ns e nt Pr oc ess ................................................................................................ 1 1 4
1 0. 1. 4. D at a Pr ot ecti o n ................................................................................................................ 1 1 4
1 0. 1. 5. C o m mitt e es Str uct ur e ...................................................................................................... 1 1 4
1 0. 1 . 6. Diss e mi n ati o n of Cli nic al St u d y D at a................................................................................. 1 1 5
1 0. 1. 7. D at a Q u alit y Ass ur a nc e .................................................................................................... 1 1 5
1 0. 1. 8. S o urc e D oc u m e nts ........................................................................................................... 1 1 7
1 0. 1. 9. St u d y a n d Sit e St art a n d Cl os ur e ....................................................................................... 1 1 7
1 0. 1. 1 0. P u blic ati o n P olic y ........................................................................................................... 1 1 8
1 0. 1. 1 1. I n v esti g at or I nf or m ati o n ................................................................................................ 1 1 8
1 0. 1. 1 2. L o n g -T er m S a m pl e R et e nti o n ......................................................................................... 1 1 8
1 0. 2. A p p e n dix 2: Cli nic al L a b or at or y T ests ......................................................................................1 1 9
1 0. 2. 1. Cli nic al L a b or at or y T ests ................................................................................................... 1 1 9
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Protocol J1P-MC-KFAH(b)
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10.2.2. Laboratory Tests to be Obtained at Time of a Systemic Hypersensitivity Event................. 124
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow up 
and Reporting..................................................................................................................................125
10.3.1. Definition of AE................................................................................................................ 125
AE Definition............................................................................................................................ 125
Events Meeting the AE Definition............................................................................................. 125
Events Not Meeting the AE Definition...................................................................................... 125
10.3.2. Definition of SAE .............................................................................................................. 126
10.3.3. Recording and Follow-Up of AE and/or SAE...................................................................... 127
AE and SAE Recording .............................................................................................................. 127
Assessment of Intensity ........................................................................................................... 127
Assessment of Causality........................................................................................................... 127
Follow-up of AEs and SAEs ....................................................................................................... 128
10.3.4. Reporting of SAEs............................................................................................................. 128
SAE Reporting via an Electronic Data Collection Tool................................................................ 128
SAE Reporting via Paper CRF.................................................................................................... 129
10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information....................... 130
10.4.1. Definitions ....................................................................................................................... 130
10.4.2. Contraception .................................................................................................................. 131
10.4.3. Collection of Pregnancy Information ................................................................................ 132
10.5. Appendix 5: Liver Safety: Hepatic Monitoring Tests.................................................................133
10.6. Appendix 6: Examples of Infections That May Be Considered Opportunistic in the Setting of 
Biologic Therapy .............................................................................................................................. 135
10.7 Appendix 7: Prohibited Medications......................................................................................... 137
10.8. Appendix 8: Permitted Medications with Dose Stabilization....................................................139
10.9. Appendix 9: Mayo Scoring System for the Assessment of Ulcerative Colitis Activity.................140
10.10. Appendix 10: Geboes Scoring for the Assessment of Histological Activity.............................. 141
10.11. Appendix 11: Patient-Reported Outcome Instruments .......................................................... 142
10.12. Appendix 12: Abbreviations ..................................................................................................144
10.13. Appendix 13: Provisions for Changes in Study Conduct During Exceptional Circumstances ....150
11. References..................................................................................................................................... 156


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Protocol J1P-MC-KFAH(b)
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1. Protocol Summary
1.1. Synopsis
Protocol Title: An Adaptive Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of 
LY3471851 (NKTR-358) in Patients with Moderately to Severely Active Ulcerative Colitis
Rationale
LY3471851 (also known as NKTR-358) is a polyethylene glycol (PEG)-conjugated recombinant 
human interleukin (IL)-2 (rhIL-2) with the capacity to promote the expansion and activation of 
regulatory T cells (Tregs) with relatively minimal effect on conventional T cells (Tcons). In 
preliminary clinical studies, other IL-2 formulations (aldesleukin and ILT-101), which are 
hypothesized to have a mechanism of action similar to that of LY3471851, were associated with 
an expansion of peripheral Tregs and biological response in patients with ulcerative colitis 
(UC).1,2 As compared to those formulations, PEGylation results in prolonged systemic exposure 
and improved binding to the high-affinity IL-2 receptor most present on Tregs.
Study J1P-MC-KFAH (KFAH) is a Phase 2 study to evaluate the efficacy and safety of multiple 
dose levels of LY3471851 in adult patients with moderately to severely active UC who have an 
inadequate response to, loss of response to, or are intolerant to conventional UC therapy 
("conventional-failed") or to advanced UC therapy ("advanced therapy-failed"). For this study, 
conventional UC therapy is defined as corticosteroids, azathioprine (AZA), or 6-mercaptopurine 
(6-MP). Results of this study will be used to guide the dose selection for future studies and to 
further characterize the benefit/risk profile of LY3471851.
Objectives and Endpoints
Objectives
Estimands/Endpoints
Primary

To determine whether LY3471851 is 
superior to placebo in inducing clinical 
remission in participants with moderately to 
severely active UC
The study will compare LY3471851 with placebo in 
participants with moderately to severely active UC.
The primary comparison of interest is the difference in the 
proportion of participants who achieve clinical remission
at Week 12.
The primary comparison will be assessed using a 
composite estimand where the intercurrent events that 
lead to permanent discontinuation of assigned study 
treatment are part of the response definition.
Secondary

To evaluate the efficacy of induction 
treatment with LY3471851 compared to 
placebo with respect to clinical, endoscopic, 
and histologic improvement
Secondary comparisons of interest are the difference 
between LY3471851 and placebo in the proportion of 
participants who have not permanently discontinued at 
Week 12 and have achieved at Week 12: 

clinical response

endoscopic remission


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Protocol J1P-MC-KFAH(b)
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Objectives
Estimands/Endpoints

endoscopic response

symptomatic remission

symptomatic response

histologic remission

histologic-endoscopic mucosal healing
Secondary comparisons with binary endpoints will use a 
composite estimand as described for the primary 
comparison.

To evaluate the efficacy of maintenance 
treatment with LY3471851 compared to 
placebo with respect to clinical, endoscopic, 
and histologic improvement
Secondary comparisons of interest include the difference 
between LY3471851 and placebo in the proportion of 
participants who were responders at Week 12 (Week 12 
Responders) and have not permanently discontinued at 
Week 52, who at Week 52 still have 

clinical remission

clinical response 

endoscopic remission

endoscopic response

symptomatic remission

symptomatic response

histologic remission

histologic-endoscopic mucosal healing
Secondary comparisons with binary endpoints will use a 
composite estimand as described for the primary 
comparison.

To evaluate the efficacy of treatment with 
LY3471851 compared to placebo with 
respect to patient-reported outcomes and 
quality of life measures
Comparison of mean changes from baseline to Week 12 
and to Week 52 in scores for

IBDQ

Urgency NRS

Abdominal Pain NRS

Nocturnal Stools

Bristol Stool Scale

PGR-S

Fatigue NRS
Secondary comparisons with continuous endpoints will 
use a hypothetical efficacy estimand strategy to address 
the intercurrent events of early discontinuation to assess 
the effect of study treatment in a hypothetical trial where 
all participants have complete data and continue to take 
study treatment without discontinuing from the study.


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Pr ot oc ol  J 1 P-M C -K F A H( b)
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O bjecti ves
Esti m a n ds/ E n d p oi nts

T o e val uate t he P K of L Y 3 4 7 1 8 5 1

Wee k 1 2 L Y 3 4 7 1 8 5 1 tr o u g h c o nce ntrati o ns
A b bre viati o ns: 
 I B D Q = I nfla m mat or y B o wel Disease Q uesti o n naire; N R S = 
n u meric rati n g scale; P G R -S = Patie nt’s Gl o bal Rati n g of Se verit y; U C = ulcerati ve c olitis;
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Pr ot oc ol  J 1 P-M C -K F A H( b)
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O ver all Desi g n
St u d y  K F A H is a n a da pti ve P hase 2 m ultice nter, ra n d omize d, d o u ble -bli n d, place b o -c o ntr olle d, 
parallel- gr o u p st u d y  t o e valuate t he efficac y a n d safet y of  mul tiple d ose l e vels of L Y 3 4 7 1 8 5 1 i n 
a d ult p atie nts wit h mo d er at e l y t o se verel y act i ve U C.
T he st u d y  d uratio n f or a n i n di vi d ual partici pa nt will be a p pr o xi matel y  6 3 wee ks.

Scree ni n g: a peri o d lasti n g u p t o 5 wee ks

I n d ucti on Peri o d: a 1 2- wee k d o u ble -bli n d treat me nt peri o d

Mai nte na nce Peri o d: a 4 0-wee k bli n de d p eri o d f or Wee k 1 2 Res p o n ders
N ote: Wee k 1 2 N o nres p o n ders e nter a n e xte nsi o n, i ncl usi ve o f e xte nsi o n i n d ucti on a n d 
e xte nsi o n ma i nte na nce perio ds , wit h tr e at me nt for a t otal  of 5 2 wee ks.

P os t-treat me nt F oll o w -u p: a peri o d l ast i n g a p pr o xi matel y 6 wee ks
Discl os ure St ate me nt: T hi s is a parallel st u d y wit h a n a da pti ve desi g n i n v ol vi n g m ult i ple 
treat me nt gr o u ps. T he st u d y is partici pa nt -bli n de d a n d i n vest i gat or-bli n de d.
N u m ber of P artici p a nts: A p pr o xi matel y 2 0 0 partici pa nts ma y be ra n d omize d acr oss all st u d y 
sta ges.
I nter ve nti o n Gr o u ps a n d D ur ati o n
T his is a n a da pt i ve st u d y wi t h 2 sta ges. D uri n g Sta ge 1, a p pr o xi matel y 1 0 0 partici pa nts ma y be 
e nr o lle d. T he i nter ve nt i on gr o u ps i n Sta ge 1 are

 µ g L Y 3 4 7 1 8 5 1 Q 2 W S C

 µ g L Y 3 4 7 1 8 5 1 Q 2 W S C , a n d

pl ace b o
D uri n g Sta ge 2, a p pr o xi matel y 1 0 0 a d dit i onal partici pa nts ma y be e nr olle d. Base d o n res ults of 
a n i nteri m a nal ysis, t he i nter ve nt i on gr o u ps i n Sta ge 2 ma y i ncl u de

pl ace b o

1, 2 , or n o ne of t he L Y 3 4 7 1 8 5 1 d oses liste d f or Sta ge 1, as well as p ossi bl y

1 or m ore a d di tio nal  L Y 3 4 7 1 8 5 1 d ose s, n o t e xcee di n g
µ g ; als o gi ve n Q 2 W S C.
F or a n y  in di vi d ual st u d y  p artici pa nt, t he ma xi m u m d uratio n of  st u d y treat me nt is 5 2 wee ks.
D at a M o nit ori n g C o m mittee: N o
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CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
13
1.2. Schema


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
1 4
A b bre viati o ns: D = da y; D N A = de o x yri b o n ucleic aci d; E T V = earl y ter mi nati o n visit; H B V = he patitis B vir us; L Y = L Y 3 4 7 1 8 5 1; 
Q 2 W = e ver y 2 wee ks; W = Wee k; w = wee ks.
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C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
1 5
A b bre viati o ns: D N A = de o x yri b o n ucleic aci d; E T V = earl y ter mi nati o n visit; H B V = he patitis B vir us; Q 2 W = e ver y 2 wee ks; W = Wee k; w = wee ks.
N ote: T he e xte nsi o n d ose c o ul d be l o wer t ha n  
 µ g L Y 3 4 7 1 8 5 1 , base d o n i nteri m a n al yses.
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CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
16
1.3. Schedule of Activities (SoA)
1.3.1. Schedule of Activities for the Screening and Induction Treatment Periods
Table 1. Schedule of Activities for the Screening and Induction Treatment Periods of Study J1P-MC-KFAH
V1 and V9 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance and all scheduled
activities are completed prior to dosing.
For procedures at an ETV, see ETV in Table 4. 
For procedures at an unscheduled visit, see V997 in Table 4.
Visit number
V1
V2
V3
V4
V5
V6
V7
V8
V9
Comment
Weeks from randomization
–5
—
1
2
4
6
8
10
12
Study day
—
1
8
15
29
43
57
71
85
Visit interval tolerance (days)
≤35
before
V2
—
±3
±3
±3
±3
±3
±3
±3
Fasting visit
X
X
Informed consent
X
Site staff explains, participant reports 
remission/normal stool frequency
X
The purpose of UC remission question should be 
explained before the participant answers the 
question. Errors in the response cannot be corrected
after the participant saves and confirms the response.
Inclusion and exclusion criteria, review 
and confirm
X
X
Demographics
X
Preexisting conditions and medical 
history
X
Includes relevant surgical history.
Prespecified medical history
X
Indication and history of interest.
Prior treatments for indication
X
Includes all UC-specific therapies since date of 
diagnosis.
Concomitant medications
X
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
For AESIs, additional data are collected 
(Section 8.3.6).
Review modified Mayo score (MMS)
X
X
Tobacco use
X
X
Alcohol and caffeine use 
X


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
1 7
T a ble 1. Sc he d ule of A cti vities f or t he Scree ni n g a n d I n d ucti o n Tre at me nt Peri o ds of St u d y J 1 P- M C -K F A H
V 1 a n d V 9 pr oce d ures ma y be c o n d ucte d o ver m ore t ha n 1 da y as l o n g as all acti vities are c o m plete d wit hi n t he all o wa ble visit t olera nce a n d all sc he d ule d
acti vities are c o m plete d pri or t o d osi n g .
F or pr oce d ures at a n E T V , see E T V i n Ta ble 4. 
F or pr oce d ures at a n u nsc he d ule d visit , see V 9 9 7 i n Ta ble 4.
Visit n u m ber
V 1
V 2
V 3
V 4
V 5
V 6
V 7
V 8
V 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
– 5
—
1
2
4
6
8
1 0
1 2
St u d y da y
—
1
8
1 5
2 9
4 3
5 7
7 1
8 5
Visit i nter val t olera nce ( d a ys)
≤3 5
bef ore
V 2
—
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
X
P h ysic al E v al u ati o n
Hei g ht
X
Partici pa nt s h o ul d re m o ve s h oes.
Wei g ht
X
X
Vital si g ns
X  
X  
X  
X  
X  
X  
X  
X  
X
Bl o o d press ure, b o d y te m perat ure, a n d p ulse rate . 
Vital si g ns s h o ul d be meas ure d after partic ipa nt has 
bee n sitti n g at least 5 mi n utes .
P h y sical e xa mi nati o n
X
T he c o m plete p h ysical e xa m e xcl u des pel vic, rectal, 
a n d breast e xa ms, u nless cli nicall y i n dicate d , a n d 
i ncl u des assess me nt f or si g ns a n d s y m pt o ms of 
t u berc ul osis ( T B), i ncl u di n g peri p heral l y m p h n o des.
See Secti o n 8. 2. 2 .
S y m pt o m -directe d p h ysical e xa mi nati o n, 
i ncl u di n g assess me nt f or si g ns a n d 
s ym pt o ms of t u berc ul osis ( T B), i ncl u di n g 
peri p heral l y m p h n o des
X
X
See Secti o n 8. 2. 2 .
X  
X
X  
X  
X
1 2 -lea d electr ocar di o gra m (E C G )
X
X
L ocall y perf or me d.
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CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
18
Table 1. Schedule of Activities for the Screening and Induction Treatment Periods of Study J1P-MC-KFAH
V1 and V9 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance and all scheduled
activities are completed prior to dosing.
For procedures at an ETV, see ETV in Table 4. 
For procedures at an unscheduled visit, see V997 in Table 4.
Visit number
V1
V2
V3
V4
V5
V6
V7
V8
V9
Comment
Weeks from randomization
–5
—
1
2
4
6
8
10
12
Study day
—
1
8
15
29
43
57
71
85
Visit interval tolerance (days)
≤35
before
V2
—
±3
±3
±3
±3
±3
±3
±3
Fasting visit
X
X
Chest x-ray (posterior-anterior view)
X
Interpreted and reported by radiologist or 
pulmonologist. Not done at screening if done within 
3 months before screening and if qualifying 
radiographs or equivalent imaging study and/or 
formal report are available for investigator’s review.
Lateral view may also be taken. Locally performed.
Patient Diary (Electronic)
Patient diary dispensed
X
Diary compliance check
X
X
X
X
X
X
X
X
Check compliance for
    Stool Frequency
    Rectal Bleeding
    Nocturnal Stools
    Bristol Stool Scale
    Urgency NRS
    Abdominal Pain NRS
    Fatigue NRS, and
    Patient Global Rating of Severity (PGR-S).
Patient-Reported Outcomes 
(Electronic)
Inflammatory Bowel Disease 
Questionnaire (IBDQ)
X
X


CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
19
Table 1. Schedule of Activities for the Screening and Induction Treatment Periods of Study J1P-MC-KFAH
V1 and V9 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance and all scheduled
activities are completed prior to dosing.
For procedures at an ETV, see ETV in Table 4. 
For procedures at an unscheduled visit, see V997 in Table 4.
Visit number
V1
V2
V3
V4
V5
V6
V7
V8
V9
Comment
Weeks from randomization
–5
—
1
2
4
6
8
10
12
Study day
—
1
8
15
29
43
57
71
85
Visit interval tolerance (days)
≤35
before
V2
—
±3
±3
±3
±3
±3
±3
±3
Fasting visit
X
X
Patient Global Impression of Change 
(PGI-C)
X
QIDS-SR16
X
X
Clinician-Administered Questionnaires 
(Paper)
Physician’s Global Assessment (PGA)
X
X
C-SSRS Screening/Baseline
X
Adapted for the assessment of ideation and behavior 
categories only.
Self-Harm Supplement Form
X
Self-Harm Follow-Up Form
X
Required if triggered by the Self-Harm Supplement 
Form per instructions.
Laboratory Tests and Sample 
Collections
Hematology
X
X
X
X
X
X
X
X
X
Clinical chemistry
X
X
X
X
X
X
X
X
X
Lipid panel
X
X
Fasting samples are preferred, but if participant is 
non fasting at time of collection, this is not a protocol 
deviation.
Urinalysis
X
X
X
X
Serum pregnancy
X
Perform only for women of childbearing potential 
and women with a history of tubal ligation.


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
2 0
T a ble 1. Sc he d ule of A cti vities f or t he Scree ni n g a n d I n d ucti o n Tre at me nt Peri o ds of St u d y J 1 P- M C -K F A H
V 1 a n d V 9 pr oce d ures ma y be c o n d ucte d o ver m ore t ha n 1 da y as l o n g as all acti vities are c o m plete d wit hi n t he all o wa ble visit t olera nce a n d all sc he d ule d
acti vities are c o m plete d pri or t o d osi n g .
F or pr oce d ures at a n E T V , see E T V i n Ta ble 4. 
F or pr oce d ures at a n u nsc he d ule d visit , see V 9 9 7 i n Ta ble 4.
Visit n u m ber
V 1
V 2
V 3
V 4
V 5
V 6
V 7
V 8
V 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
– 5
—
1
2
4
6
8
1 0
1 2
St u d y da y
—
1
8
1 5
2 9
4 3
5 7
7 1
8 5
Visit i nter val t olera nce ( d a ys)
≤3 5
bef ore
V 2
—
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
X
Ur i ne pre g na nc y (l ocal)
X
X  
X  
X
P erf or m o nl y f or w o me n of c hil d beari n g p ote ntial 
a n d w o me n wit h a hist or y of t u bal li gati o n. At d osi n g 
visits w hic h ha ve pre g na nc y testi n g, t he pre g na nc y 
test res ult m ust be c o nfir me d t o be ne gati ve pri or t o 
d osi n g . Pr e g na nc y testi n g m a y be perf or me d m ore 
fre q ue ntl y t ha n desi g nate d o n t he So A, if l ocal la ws
or  re g ulati o ns re q uire m ore fre q ue nt testi n g.
F ollicle -sti m ulati n g h or m o ne ( F S H)
X
O pti o nal, perf or m o nl y f or w o me n n ot of 
c hil d beari n g p ote ntial t o c o nfir m p ost me n o pa usal 
stat us.
X  
X  
X  
X  
X  
X  
X  
X
T u berc ul osis ( T B) test
X
Patie nts w h o ha d a t u berc uli n s ki n test ( T S T) will 
ret ur n fr o m 4 8 t o 7 2 h o urs after place me nt t o ha ve 
t he test res ult rea d. Sa m ples ma y be se nt t o ce ntral or 
l ocal la b orat or y base d o n t he t y pe of test. A l ocal 
la b orat or y m ust be q ualifie d b y l ocal re g ulati o ns.
H u ma n i m m u n o deficie nc y vir us (HI V )
scree ni n g tests
X
He patitis C vir us ( H C V) scree ni n g tests
X
H C V R N A will be meas ure d t o c o nfir m p ositi ve 
he patitis C vir us a nti b o d y.
He patitis B vir us ( H B V) scree ni n g tests
X
I ncl u des testi n g f or H Bs A g a n d a nti-H Bc .
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
2 1
T a ble 1. Sc he d ule of A cti vities f or t he Scree ni n g a n d I n d ucti o n Tre at me nt Peri o ds of St u d y J 1 P- M C -K F A H
V 1 a n d V 9 pr oce d ures ma y be c o n d ucte d o ver m ore t ha n 1 da y as l o n g as all acti vities are c o m plete d wit hi n t he all o wa ble visit t olera nce a n d all sc he d ule d
acti vities are c o m plete d pri or t o d osi n g .
F or pr oce d ures at a n E T V , see E T V i n Ta ble 4. 
F or pr oce d ures at a n u nsc he d ule d visit , see V 9 9 7 i n Ta ble 4.
Visit n u m ber
V 1
V 2
V 3
V 4
V 5
V 6
V 7
V 8
V 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
– 5
—
1
2
4
6
8
1 0
1 2
St u d y da y
—
1
8
1 5
2 9
4 3
5 7
7 1
8 5
Visit i nter val t olera nce ( d a ys)
≤3 5
bef ore
V 2
—
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
X
H B V D N A
X
X
O nl y f or partici pa nts w h o are p ositi ve f or a nti ‑ H Bc 
at scree ni n g .
P har mac o ki netic ( P K) sa m ples
X  
X  
X  
X  
X  
X
C ollect sa m ples bef ore d osi n g, if d osi n g is 
sc he d ule d. C ollect a d diti o nal sa m ples at s pecifie d 
ti mes relati ve t o o nset of h y perse nsiti vit y e ve nts.
X  
X  
X  
X  
X
C ollect sa m ples bef ore d osi n g, if d osi n g is 
sc he d ule d. C ollect a d diti o nal sa m ples at s pecifie d 
ti mes relati ve t o o nset of h y perse nsiti vit y e ve nts.
Fl o w c yt o metr y pa nel
X  
X
X
G e netics sa m ple
X
Bl o o d sa m ple f or D N A p har mac o ge netics ca n be 
o btai ne d a n y ti me at or after V 2.
X
X  
X  
X
E n d osc o pic Pr oce d ure
E n d osc o p y
X
X
Scree ni n g e n d osc o p y m ust occ ur ≤1 4 da ys pri or t o 
ra n d o mizati o n. At scree ni n g, perf or m o nl y f or 
partici pa nts w h o are eli gi ble f or t he st u d y b y all ot her 
st u d y e ntr y criteria.
C ol o n bi o ps y sa m ple c ollecti o n
X
X
Perf or me d at ti me of e n d osc o p y. Instr ucti o n s f or 
c ollecti o n are pr o vi de d i n t he la b ma n ual. Fle xi ble 
si g m oi d osc o p y is rec o m me n de d, e xce pt f or 
pr ot oc ol -s pecifie d reas o ns w he n a c ol o n osc o p y 
s h o ul d be perf or me d.
C CI
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C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
2 2
T a ble 1. Sc he d ule of A cti vities f or t he Scree ni n g a n d I n d ucti o n Tre at me nt Peri o ds of St u d y J 1 P- M C -K F A H
V 1 a n d V 9 pr oce d ures ma y be c o n d ucte d o ver m ore t ha n 1 da y as l o n g as all acti vities are c o m plete d wit hi n t he all o wa ble visit t olera nce a n d all sc he d ule d
acti vities are c o m plete d pri or t o d osi n g .
F or pr oce d ures at a n E T V , see E T V i n Ta ble 4. 
F or pr oce d ures at a n u nsc he d ule d visit , see V 9 9 7 i n Ta ble 4.
Visit n u m ber
V 1
V 2
V 3
V 4
V 5
V 6
V 7
V 8
V 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
– 5
—
1
2
4
6
8
1 0
1 2
St u d y da y
—
1
8
1 5
2 9
4 3
5 7
7 1
8 5
Visit i nter val t olera nce ( d a ys)
≤3 5
bef ore
V 2
—
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
X
St o ol S a m ples
St o ol cult ur e
X
A d diti o nal l ocal st o ol testi n g (f or e xa m ple, f or o va 
a n d parasites) is all o we d at t he i n vesti gat or’s 
discreti o n.
C. difficile testi n g
X
A d diti o nal C. difficile testi n g is all o we d t hr o u g h o ut
t he st u d y at t he i n vesti gat or’s discreti o n .
X
X  
X  
X
X
X  
X  
X
R a n d o miz ati o n a n d D osi n g
Ra n d o mizati o n
X
D osi n g
X  
X  
X  
X  
X  
X  
X
N o d osi n g at V 3.
A b bre viati o ns: A E SIs = a d verse e ve nt of s pecial i nterest; a nti -H Bc = a nti b o d y t o he patitis B c ore a nti ge n; C- S S R S = C ol u m bia – S uici de Se verit y Rati n g Scale ; 
D N A = de o x yri b o n ucleic aci d; E T V = earl y ter mi nati o n visit; N R S = n u meric rati n g scale; H Bs A g = he patitis B s urface a nti ge n; QI D S -S R 1 6 = 1 6 -Ite m 
Q uic k I n ve nt or y of De pressi ve S y m pt o mat ol o g y – Self Re p ort; R N A = ri b o n ucleic aci d ; S o A = sc he d ule of acti vities; U C = ulcerati ve c olitis; V = visit.
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
2 3
1. 3. 2. Sc he d ule of Acti vities f or t he M ai nte n a nce Tre at me n t Peri o d
T a ble 2. Sc he d ule of A cti vities f or t he M ai nte n a nce Tre at me nt
Peri o d of St u d y J 1 P- M C -K F A H
T his sc he d ule a p plies t o st u d y partici pa nts w h o are res p o n ders at Wee k 1 2.
F or pr oce d ures at a n E T V , see E T V i n Ta ble 4. 
F or pr oce d ures at a n u nsc he d ule d visit , see V 9 9 7 i n Ta ble 4.
Visits 1 0 t hr o u g h 2 8 are eli gi ble t o be c o n d ucte d re m otel y (t hat is, b y tele p h o ne, I T-assiste d virt ual visit, m o bile healt hcare, or a c o m bi nati o n t here of), if writte n 
a p pr o val is pr o vi de d b y t he s p o ns or a n d acc or di n g t o t he pref ere nces of t he partici pa nt a n d t he st u d y site. H o we ver, n o m ore t ha n 3 4 da ys ca n ela pse wit h o ut a n 
o n -site st u d y visit occ urri n g.
Visit n u m ber
V 1 0
V 1 1
V 1 2
V 1 3
V 1 4
V 1 5
V 1 6
V 1 7
V 1 8
V 1 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
1 4
1 6
1 8
2 0
2 2
2 4
2 6
2 8
3 0
3 2
St u d y d a y
9 9
1 1 3
1 2 7
1 4 1
1 5 5
1 6 9
1 8 3
1 9 7
2 1 1
2 2 5
Visit i nter val t olera nce ( d a ys)
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
C o nc o mita nt me dicati o ns
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
A d verse e ve nts
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
F or A E SIs, a d diti o nal data are c ollecte d 
( Secti o n 8. 3. 6 ).
T o bacc o use
X
P h ysic al E v al u ati o n
Wei g ht
X
Vital si g ns
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Bl o o d press ure, b o d y te m perat ure, a n d 
p ulse rate. Vital si g ns s h o ul d be 
meas ure d after partic ipa nt has bee n 
sitti n g f or at least 5 mi n utes.
S y m pt o m -directe d p h ysical e xa mi nati o n ,
i ncl u di n g assess me nt f or si g ns a n d 
s ym pt o ms of t u berc ul osis ( T B), i ncl u di n g 
peri p heral l y m p h n o des
X
See Secti o n 8. 2. 2 .
X
1 2 -lea d electr ocar di o gra m (E C G )
X
L ocall y perf or me d.
P atie nt Di ar y ( Electr o nic)
C CI


CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
24
Table 2. Schedule of Activities for the Maintenance Treatment Period of Study J1P-MC-KFAH
This schedule applies to study participants who are responders at Week 12.
For procedures at an ETV, see ETV in Table 4. 
For procedures at an unscheduled visit, see V997 in Table 4.
Visits 10 through 28 are eligible to be conducted remotely (that is, by telephone, IT-assisted virtual visit, mobile healthcare, or a combination thereof), if written 
approval is provided by the sponsor and according to the preferences of the participant and the study site. However, no more than 34 days can elapse without an 
on-site study visit occurring.
Visit number
V10
V11
V12
V13
V14
V15
V16
V17
V18
V19
Comment
Weeks from randomization
14
16
18
20
22
24
26
28
30
32
Study day
99
113
127
141
155
169
183
197
211
225
Visit interval tolerance (days)
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
Fasting visit
X
Diary compliance check
X
X
X
X
X
X
X
X
X
X
Check compliance for
  Stool Frequency
  Rectal Bleeding
  Nocturnal Stools
  Bristol Stool Scale
  Urgency NRS
  Abdominal Pain NRS
  Fatigue NRS, and
  Patient Global Rating of Severity 
(PGR-S).
Patient-Reported Outcomes 
(Electronic)
Inflammatory Bowel Disease 
Questionnaire (IBDQ)
X
Patient Global Impression of Change 
(PGI-C)
X
QIDS-SR16
X
Laboratory Tests and Sample 
Collections
Hematology
X
X
X
X
X
Clinical chemistry
X
X
X
X
X


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
2 5
T a ble 2. Sc he d ule of A cti vities f or t he M ai nte n a nce Tre at me nt
Peri o d of St u d y J 1 P- M C -K F A H
T his sc he d ule a p plies t o st u d y partici pa nts w h o are res p o n ders at Wee k 1 2.
F or pr oce d ures at a n E T V , see E T V i n Ta ble 4. 
F or pr oce d ures at a n u nsc he d ule d visit , see V 9 9 7 i n Ta ble 4.
Visits 1 0 t hr o u g h 2 8 are eli gi ble t o be c o n d ucte d re m otel y (t hat is, b y tele p h o ne, I T-assiste d virt ual visit, m o bile healt hcare, or a c o m bi nati o n t here of), if writte n 
a p pr o val is pr o vi de d b y t he s p o ns or a n d acc or di n g t o t he pref ere nces of t he partici pa nt a n d t he st u d y site. H o we ver, n o m ore t ha n 3 4 da ys ca n ela pse wit h o ut a n 
o n -site st u d y visit occ urri n g.
Visit n u m ber
V 1 0
V 1 1
V 1 2
V 1 3
V 1 4
V 1 5
V 1 6
V 1 7
V 1 8
V 1 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
1 4
1 6
1 8
2 0
2 2
2 4
2 6
2 8
3 0
3 2
St u d y d a y
9 9
1 1 3
1 2 7
1 4 1
1 5 5
1 6 9
1 8 3
1 9 7
2 1 1
2 2 5
Visit i nter val t olera nce ( d a ys)
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
Li pi d pa nel
X
Fasti n g sa m ples are preferre d, b ut if 
partici pa nt is n onfasti n g at ti me of 
c ollecti o n, t his is n ot a pr ot oc ol 
de viati o n.
Ur i nal ysis
X
X
X
Ur i ne pre g na nc y (l ocal)
X
X
X
X
X
P erf or m o nl y f or w o me n of 
c hil d beari n g p ote ntial a n d w o me n wit h 
a hist or y of t u bal li gati o n. At d osi n g 
visits w hic h ha ve pre g na nc y testi n g, t he 
pre g na nc y test res ult m ust be c o nfir me d 
t o be ne gati ve pri or t o d osi n g . 
Pre g na nc y testi n g m a y be perf or me d 
m ore fre q ue nt l y t ha n desi g nate d o n t he 
S o A, if l ocal la ws or  re g ulati o ns re q uire 
m ore fre q ue nt testi n g.
X
H B V D N A
X
O nl y f or partici pa nts w h o are p ositi ve 
f or a nti‑ H Bc at scree ni n g.
P har mac o ki netic ( P K) sa m ples
X
C ollect sa m ples bef ore d osi n g, if 
d osi n g is sc he d ule d. C ollect a d diti o nal 
sa m ples at s pecifie d ti mes relati ve t o 
o nset of h y perse nsiti vit y e ve nts.
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
2 6
T a ble 2. Sc he d ule of A cti vities f or t he M ai nte n a nce Tre at me nt
Peri o d of St u d y J 1 P- M C -K F A H
T his sc he d ule a p plies t o st u d y partici pa nts w h o are res p o n ders at Wee k 1 2.
F or pr oce d ures at a n E T V , see E T V i n Ta ble 4. 
F or pr oce d ures at a n u nsc he d ule d visit , see V 9 9 7 i n Ta ble 4.
Visits 1 0 t hr o u g h 2 8 are eli gi ble t o be c o n d ucte d re m otel y (t hat is, b y tele p h o ne, I T-assiste d virt ual visit, m o bile healt hcare, or a c o m bi nati o n t here of), if writte n 
a p pr o val is pr o vi de d b y t he s p o ns or a n d acc or di n g t o t he pref ere nces of t he partici pa nt a n d t he st u d y site. H o we ver, n o m ore t ha n 3 4 da ys ca n ela pse wit h o ut a n 
o n -site st u d y visit occ urri n g.
Visit n u m ber
V 1 0
V 1 1
V 1 2
V 1 3
V 1 4
V 1 5
V 1 6
V 1 7
V 1 8
V 1 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
1 4
1 6
1 8
2 0
2 2
2 4
2 6
2 8
3 0
3 2
St u d y d a y
9 9
1 1 3
1 2 7
1 4 1
1 5 5
1 6 9
1 8 3
1 9 7
2 1 1
2 2 5
Visit i nter val t olera nce ( d a ys)
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
X
C ollect sa m ples bef ore d osi n g, if
d osi n g is sc he d ule d. C ollect a d diti o nal 
sa m ples at s pecifie d ti mes relati ve t o 
o nset of h y perse nsiti vit y e ve nts.
Fl o w c yt o metr y pa nel
X
G e netics sa m ple
Bl o o d sa m ple f or D N A 
p har mac o ge netics ca n be o btai ne d a n y 
ti me at or after V 2.
X
E n d osc o pic Pr oce d ure
N ot a p plica ble f or res p o n ders d uri n g 
t he ti me peri o d of V 1 0 t hr o u g h V 1 9
St o ol S a m ples
X
X
R a n d o miz ati o n a n d D osi n g
D osi n g
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
C CI
C CI
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
2 7
T a ble 2 (c o nti n ue d). Sc he d ule of acti vities f or t he M ai nte n a nce Tre at me nt
P eri o d of St u d y J 1 P- M C -K F A H
T his sc he d ule a p plies t o st u d y partici pa nts w h o are res p o n ders at Wee k 1 2.
F or pr oce d ures at a n earl y ter mi nati o n visit, see E T V i n Ta ble 4. 
F or pr oce d ures at a n u nsc he d ule d visit , see V 9 9 7 i n Ta ble 4.
Visits 1 0 t hr o u g h 2 8 are eli gi ble t o be c o n d ucte d re m otel y (t hat is, b y tele p h o ne, I T-assiste d virt ual visit, m o bile healt hcare, or a c o m bi nati o n t here of) if writte n a p pr o val 
is pr o vi de d b y t he s p o ns or a n d acc or di n g t o t he prefere nces of t he partici pa nt a n d t he st u d y site. H o we ver, n o m ore t ha n 3 4 da ys ca n ela pse wit h o ut a n o n-site st u d y visit 
occ urri n g.
Visit n u m ber
V 2 0
V 2 1
V 2 2
V 2 3
V 2 4
V 2 5
V 2 6
V 2 7
V 2 8
V 2 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
3 4
3 6
3 8
4 0
4 2
4 4
4 6
4 8
5 0
5 2
St u d y da y
2 3 9
2 5 3
2 6 7
2 8 1
2 9 5
3 0 9
3 2 3
3 3 7
3 5 1
3 6 5
Visit i nter val t olera nce ( d a ys)
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
C o nc o mita nt me dicati o ns
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
A d verse e ve nts
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
F or A E SIs, a d diti o nal data are c ollecte d 
( Secti o n 8. 3. 6 ).
Re vie w m o difie d Ma y o sc ore ( M M S)
X
T o bacc o use
X
P h y sical E val uati o n
Wei g ht
X
Vital si g ns
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Bl o o d press ure, b o d y te m perat ure, a n d p ulse 
rate. Vital si g ns s h o ul d be meas ure d after 
partic ipa nt has bee n sitti n g f or at least 5 
mi n utes.
S y m pt o m -directe d p h ysical e xa mi nati o n ,
i ncl u di n g assess me nt f or si g ns a n d 
s ym pt o ms of t u berc ul osis ( T B), 
i ncl u di n g peri p heral l y m p h n o des
X
X
See Secti o n 8. 2. 2 .
X
X
1 2 -lea d electr ocar di o gra m (E C G )
X
L ocall y perf or me d.
C CI


CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
28
Table 2 (continued). Schedule of activities for the Maintenance Treatment Period of Study J1P-MC-KFAH
This schedule applies to study participants who are responders at Week 12.
For procedures at an early termination visit, see ETV in Table 4. 
For procedures at an unscheduled visit, see V997 in Table 4.
Visits 10 through 28 are eligible to be conducted remotely (that is, by telephone, IT-assisted virtual visit, mobile healthcare, or a combination thereof) if written approval 
is provided by the sponsor and according to the preferences of the participant and the study site. However, no more than 34 days can elapse without an on-site study visit 
occurring.
Visit number
V20
V21
V22
V23
V24
V25
V26
V27
V28
V29
Comment
Weeks from randomization
34
36
38
40
42
44
46
48
50
52
Study day
239
253
267
281
295
309
323
337
351
365
Visit interval tolerance (days)
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
Fasting visit
X
Patient Diary (Electronic)
Diary compliance check
X
X
X
X
X
X
X
X
X
X
Check compliance for
  Stool Frequency
  Rectal Bleeding
  Nocturnal Stools
  Bristol Stool Scale
  Urgency NRS
  Abdominal Pain NRS
  Fatigue NRS, and
  Patient Global Rating of Severity (PGR-S).
Diary return
X
Patient-Reported Outcomes 
(Electronic)
Inflammatory Bowel Disease 
Questionnaire (IBDQ)
X
Patient Global Impression of Change 
(PGI-C)
X
QIDS-SR16
X
Clinician-Administered 
Questionnaires (Paper)
Physician’s Global Assessment (PGA)
X


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
2 9
T a ble 2 (c o nti n ue d). Sc he d ule of acti vities f or t he M ai nte n a nce Tre at me nt
P eri o d of St u d y J 1 P- M C -K F A H
T his sc he d ule a p plies t o st u d y partici pa nts w h o are res p o n ders at Wee k 1 2.
F or pr oce d ures at a n earl y ter mi nati o n visit, see E T V i n Ta ble 4. 
F or pr oce d ures at a n u nsc he d ule d visit , see V 9 9 7 i n Ta ble 4.
Visits 1 0 t hr o u g h 2 8 are eli gi ble t o be c o n d ucte d re m otel y (t hat is, b y tele p h o ne, I T-assiste d virt ual visit, m o bile healt hcare, or a c o m bi nati o n t here of) if writte n a p pr o val 
is pr o vi de d b y t he s p o ns or a n d acc or di n g t o t he prefere nces of t he partici pa nt a n d t he st u d y site. H o we ver, n o m ore t ha n 3 4 da ys ca n ela pse wit h o ut a n o n-site st u d y visit 
occ urri n g.
Visit n u m ber
V 2 0
V 2 1
V 2 2
V 2 3
V 2 4
V 2 5
V 2 6
V 2 7
V 2 8
V 2 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
3 4
3 6
3 8
4 0
4 2
4 4
4 6
4 8
5 0
5 2
St u d y da y
2 3 9
2 5 3
2 6 7
2 8 1
2 9 5
3 0 9
3 2 3
3 3 7
3 5 1
3 6 5
Visit i nter val t olera nce ( d a ys)
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
L a b or at or y Tests a n d S a m ple 
C ollecti o ns
He mat ol o g y
X
X
X
X
X
Cli nical c he mistr y
X
X
X
X
X
Li pi d pa nel
X
Fasti n g sa m ples are preferre d, b ut if 
partici pa nt is n onfasti n g at ti me of c ollecti o n, 
t his is n ot a pr ot oc ol de viati o n.
Ur i nal ysis
X
Ur i ne pre g na nc y (l ocal)
X
X
X
X
X
P erf or m o nl y f or w o me n of c hil d beari n g 
p ote ntial a n d w o me n wit h a hist or y of t u bal 
li gati on. At d osi n g visits w hic h ha ve 
pre g na nc y testi n g, t he pre g na nc y test res ult 
m ust be c o nfir me d t o be ne gati ve pri or t o 
d osi n g . Pr e g na nc y testi n g m a y be perf or me d 
m ore fre q ue nt l y t ha n desi g nate d o n t he So A,
if l ocal la ws or  re g ulati o ns re q uire m ore 
fre q ue nt testi n g.
X
H B V D N A
X
X
O nl y f or partici pa nts w h o are p ositi ve f or 
a nti ‑ H Bc at scree ni n g.
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
3 0
T a ble 2 (c o nti n ue d). Sc he d ule of acti vities f or t he M ai nte n a nce Tre at me nt
P eri o d of St u d y J 1 P- M C -K F A H
T his sc he d ule a p plies t o st u d y partici pa nts w h o are res p o n ders at Wee k 1 2.
F or pr oce d ures at a n earl y ter mi nati o n visit, see E T V i n Ta ble 4. 
F or pr oce d ures at a n u nsc he d ule d visit , see V 9 9 7 i n Ta ble 4.
Visits 1 0 t hr o u g h 2 8 are eli gi ble t o be c o n d ucte d re m otel y (t hat is, b y tele p h o ne, I T-assiste d virt ual visit, m o bile healt hcare, or a c o m bi nati o n t here of) if writte n a p pr o val 
is pr o vi de d b y t he s p o ns or a n d acc or di n g t o t he prefere nces of t he partici pa nt a n d t he st u d y site. H o we ver, n o m ore t ha n 3 4 da ys ca n ela pse wit h o ut a n o n-site st u d y visit 
occ urri n g.
Visit n u m ber
V 2 0
V 2 1
V 2 2
V 2 3
V 2 4
V 2 5
V 2 6
V 2 7
V 2 8
V 2 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
3 4
3 6
3 8
4 0
4 2
4 4
4 6
4 8
5 0
5 2
St u d y da y
2 3 9
2 5 3
2 6 7
2 8 1
2 9 5
3 0 9
3 2 3
3 3 7
3 5 1
3 6 5
Visit i nter val t olera nce ( d a ys)
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
P har mac o ki netic ( P K) sa m ples
X
X
C ollect sa m ples bef ore d osi n g, if d osi n g is 
sc he d ule d. C ollect a d diti o nal sa m ples at 
s pecifie d ti mes relati ve t o o nset of 
h y perse nsiti vit y e ve nts.
X
X
C ollect sa m ples bef ore d osi n g, if d osi n g is 
sc he d ule d. C ollect a d diti o nal sa m ples at 
s pecifie d ti mes relati ve t o o nset of 
h y perse nsiti vit y e ve nts.
Fl o w c yt o metr y pa nel
X
G e netics sa m ple
Bl o o d sa m ple f or D N A p har mac o ge netics ca n 
be o btai ne d a n y ti me at or after V 2.
X
X
E n d osc o pic Pr oce d ure
E n d osc o p y
X
C ol o n bi o ps y sa m ple c ollecti o n
X
Perf or me d at ti me of e n d osc o p y. Instr ucti o n s
f or c ollecti o n are pr o vi de d i n t he la b ma n ual. 
Fle xi ble si g m oi d osc o p y is rec o m me n de d, 
e xce pt f or pr ot oc ol -s pecifie d reas o ns w he n a 
c ol o n osc o p y s h o ul d be perf or me d.
St o ol S a m ples
X
X
X
X
C CI
C CI
C CI


CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
31
Table 2 (continued). Schedule of activities for the Maintenance Treatment Period of Study J1P-MC-KFAH
This schedule applies to study participants who are responders at Week 12.
For procedures at an early termination visit, see ETV in Table 4. 
For procedures at an unscheduled visit, see V997 in Table 4.
Visits 10 through 28 are eligible to be conducted remotely (that is, by telephone, IT-assisted virtual visit, mobile healthcare, or a combination thereof) if written approval 
is provided by the sponsor and according to the preferences of the participant and the study site. However, no more than 34 days can elapse without an on-site study visit 
occurring.
Visit number
V20
V21
V22
V23
V24
V25
V26
V27
V28
V29
Comment
Weeks from randomization
34
36
38
40
42
44
46
48
50
52
Study day
239
253
267
281
295
309
323
337
351
365
Visit interval tolerance (days)
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
Fasting visit
X
Randomization and Dosing
Dosing
X
X
X
X
X
X
X
X
X
No dosing at V29.
Abbreviations: AESIs = adverse event of special interest; anti-HBc = antibody to hepatitis B core antigen; DNA = deoxyribonucleic acid; ETV = early 
termination visit; HBV = hepatitis B virus; IT = information technology; NRS = numeric rating scale; QIDS-SR16 = 16-Item Quick Inventory of Depressive 
Symptomatology–Self Report; SoA = schedule of activities; V = visit.


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
3 2
1. 3. 3. Sc he d ule of Acti vities f or t he E xte nsi o n I n d ucti o n a n d E xte nsi o n M ai nte n a nce Peri o d s
T a ble 3. Sc he d ule of A cti vities f or t he E xte nsi o n I n d ucti o n a n d E xte nsi o n M ai nte n a nce Tre at me nt Peri o ds of St u d y J 1 P- M C -K F A H
T his sc he d ule a p plies t o st u d y partici pa nts w h o are n o nr es p o n ders at Wee k 1 2.
V 1 6 pr oce d ures ma y be c o n d ucte d o ver m ore t ha n 1 da y as l o n g as all acti vities are c o m plete d wit hi n t he all o wa ble visit t olera nce a n d all sc he d ule d acti vities are 
c o m plete d pri or t o d osi n g
F or pr oce d ures at a n E T V , see E T V i n Ta ble 4. 
F or pr oce d ures at a n u ns c h e d ule d visit , see V 9 9 7 i n Ta ble 4.
Visits 1 7 t hr o u g h 2 8 are eli gi ble t o be c o n d ucte d re m otel y (t hat is, b y tele p h o ne, I T-assiste d virt ual visit, m o bile healt hcare, or a c o m bi nati o n t here of) if writte n 
a p pr o val is pr o vi de d b y t he s p o ns or a n d acc or di n g t o t he prefere nces of t he partici pa nt a n d t he st u d y site. H o we ver, n o m ore t ha n 3 4 da ys ca n ela pse wit h o ut a n 
o n -site st u d y visit occ urri n g.
Visit n u m ber
V 1 0
V 1 1
V 1 2
V 1 3
V 1 4
V 1 5
V 1 6
V 1 7
V 1 8
V 1 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
1 4
1 6
1 8
2 0
2 2
2 4
2 6
2 8
3 0
3 2
St u d y da y
9 9
1 1 3
1 2 7
1 4 1
1 5 5
1 6 9
1 8 3
1 9 7
2 1 1
2 2 5
Visit i nter val t olera nce ( d a ys)
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
C o nc o mita nt me dicati o ns
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
A d verse e ve nts
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
F or A E SIs, a d diti o nal data are c ollecte d
( Secti o n 8. 3. 6 ).
Re vie w m o difie d Ma y o sc ore ( M M S)
X
T o bacc o use
X
P h ysic al E v al u ati o n
Wei g ht
X
X
Vital si g ns
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Bl o o d press ure, b o d y te m perat ure, a n d 
p ulse rate. Vital si g ns s h o ul d be 
meas ure d after partic ipa nt has bee n 
sitti n g f or at least 5 mi n utes.
S y m pt o m -directe d p h ysical e xa mi nati o n ,
i ncl u di n g assess me nt f or si g ns a n d 
s ym pt o ms of t u berc ul osis ( T B), i ncl u di n g 
peri p heral l y m p h n o des
X
X
See Secti o n 8. 2. 2 .
X
X
X
X
1 2 -lea d electr ocar di o gra m (E C G )
X
X
L ocall y perf or me d.
P atie nt Di ar y ( Electr o nic)
C CI


CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
33
Table 3. Schedule of Activities for the Extension Induction and Extension Maintenance Treatment Periods of Study J1P-MC-KFAH
This schedule applies to study participants who are nonresponders at Week 12.
V16 procedures may be conducted over more than 1 day as long as all activities are completed within the allowable visit tolerance and all scheduled activities are 
completed prior to dosing
For procedures at an ETV, see ETV in Table 4. 
For procedures at an unscheduled visit, see V997 in Table 4.
Visits 17 through 28 are eligible to be conducted remotely (that is, by telephone, IT-assisted virtual visit, mobile healthcare, or a combination thereof) if written 
approval is provided by the sponsor and according to the preferences of the participant and the study site. However, no more than 34 days can elapse without an 
on-site study visit occurring.
Visit number
V10
V11
V12
V13
V14
V15
V16
V17
V18
V19
Comment
Weeks from randomization
14
16
18
20
22
24
26
28
30
32
Study day
99
113
127
141
155
169
183
197
211
225
Visit interval tolerance (days)
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
Fasting visit
X
Diary compliance check
X
X
X
X
X
X
X
X
X
X
Check compliance for
  Stool Frequency
  Rectal Bleeding
  Nocturnal Stools
  Bristol Stool Scale
  Urgency NRS
  Abdominal Pain NRS
  Fatigue NRS, and
  Patient Global Rating of Severity 
(PGR-S).
Patient-Reported Outcomes 
(Electronic)
Inflammatory Bowel Disease 
Questionnaire (IBDQ)
X
Patient Global Impression of Change 
(PGI-C)
X
QIDS-SR16
X
Clinician-Administered Questionnaires 
(Paper)
Physician’s Global Assessment (PGA)
X


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
3 4
T a ble 3. Sc he d ule of A cti vities f or t he E xte nsi o n I n d ucti o n a n d E xte nsi o n M ai nte n a nce Tre at me nt Peri o ds of St u d y J 1 P- M C -K F A H
T his sc he d ule a p plies t o st u d y partici pa nts w h o are n o nr es p o n ders at Wee k 1 2.
V 1 6 pr oce d ures ma y be c o n d ucte d o ver m ore t ha n 1 da y as l o n g as all acti vities are c o m plete d wit hi n t he all o wa ble visit t olera nce a n d all sc he d ule d acti vities are 
c o m plete d pri or t o d osi n g
F or pr oce d ures at a n E T V , see E T V i n Ta ble 4. 
F or pr oce d ures at a n u ns c h e d ule d visit , see V 9 9 7 i n Ta ble 4.
Visits 1 7 t hr o u g h 2 8 are eli gi ble t o be c o n d ucte d re m otel y (t hat is, b y tele p h o ne, I T-assiste d virt ual visit, m o bile healt hcare, or a c o m bi nati o n t here of) if writte n 
a p pr o val is pr o vi de d b y t he s p o ns or a n d acc or di n g t o t he prefere nces of t he partici pa nt a n d t he st u d y site. H o we ver, n o m ore t ha n 3 4 da ys ca n ela pse wit h o ut a n 
o n -site st u d y visit occ urri n g.
Visit n u m ber
V 1 0
V 1 1
V 1 2
V 1 3
V 1 4
V 1 5
V 1 6
V 1 7
V 1 8
V 1 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
1 4
1 6
1 8
2 0
2 2
2 4
2 6
2 8
3 0
3 2
St u d y da y
9 9
1 1 3
1 2 7
1 4 1
1 5 5
1 6 9
1 8 3
1 9 7
2 1 1
2 2 5
Visit i nter val t olera nce ( d a ys)
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
L a b or at or y Tests a n d S a m ple 
C ollecti o ns
He mat ol o g y
X  
X  
X  
X  
X  
X  
X  
X
X
Cli nical c he mistr y
X  
X  
X  
X  
X  
X  
X  
X
X
Li pi d pa nel
X
Fasti n g sa m ples are preferre d, b ut if 
partici pa nt is n onfasti n g at ti me of 
c ollecti o n, t his is n ot a pr ot oc ol 
de viati o n.
Ur i nal ysis
X  
X  
X  
X  
X
X
Ur i ne pre g na nc y (l ocal)
X
X
X
X
X
P erf or m o nl y f or w o me n of 
c hil d beari n g p ote ntial a n d w o me n wit h 
a hist or y of t u bal li gati o n. At d osi n g 
visits w hic h ha ve pre g na nc y testi n g, t he 
pre g na nc y test res ult m ust be c o nfir me d 
t o be ne gati ve pri or t o d osi n g . 
Pre g na nc y testi n g m a y be perf or me d 
m ore fre q ue ntl y t ha n desi g nate d o n t he 
S o A if l ocal la w s or  re g ulati o ns re q uire 
m ore fre q ue nt test i n g.
X
X
X
X
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
3 5
T a ble 3. Sc he d ule of A cti vities f or t he E xte nsi o n I n d ucti o n a n d E xte nsi o n M ai nte n a nce Tre at me nt Peri o ds of St u d y J 1 P- M C -K F A H
T his sc he d ule a p plies t o st u d y partici pa nts w h o are n o nr es p o n ders at Wee k 1 2.
V 1 6 pr oce d ures ma y be c o n d ucte d o ver m ore t ha n 1 da y as l o n g as all acti vities are c o m plete d wit hi n t he all o wa ble visit t olera nce a n d all sc he d ule d acti vities are 
c o m plete d pri or t o d osi n g
F or pr oce d ures at a n E T V , see E T V i n Ta ble 4. 
F or pr oce d ures at a n u ns c h e d ule d visit , see V 9 9 7 i n Ta ble 4.
Visits 1 7 t hr o u g h 2 8 are eli gi ble t o be c o n d ucte d re m otel y (t hat is, b y tele p h o ne, I T-assiste d virt ual visit, m o bile healt hcare, or a c o m bi nati o n t here of) if writte n 
a p pr o val is pr o vi de d b y t he s p o ns or a n d acc or di n g t o t he prefere nces of t he partici pa nt a n d t he st u d y site. H o we ver, n o m ore t ha n 3 4 da ys ca n ela pse wit h o ut a n 
o n -site st u d y visit occ urri n g.
Visit n u m ber
V 1 0
V 1 1
V 1 2
V 1 3
V 1 4
V 1 5
V 1 6
V 1 7
V 1 8
V 1 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
1 4
1 6
1 8
2 0
2 2
2 4
2 6
2 8
3 0
3 2
St u d y da y
9 9
1 1 3
1 2 7
1 4 1
1 5 5
1 6 9
1 8 3
1 9 7
2 1 1
2 2 5
Visit i nter val t olera nce ( d a ys)
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
H B V D N A
X
O nl y f or partici pa nts w h o are p ositi ve 
f or a nti‑ H Bc at scree ni n g.
P har mac o ki netic ( P K) sa m ples
X
C ollect sa m ples bef ore d osi n g, if
d osi n g is sc he d ule d. C ollect a d diti o nal 
sa m ples at s pecifie d ti mes relati ve t o 
o nset of h y perse nsiti vit y e ve nts.
X
C ollect sa m ples bef ore d osi n g, if
d osi n g is sc he d ule d. C ollect a d diti o nal 
sa m ples at s pecifie d ti mes relati ve t o 
o nset of h y perse nsiti vit y e ve nts.
Fl o w c yt o metr y pa nel
X
G e netics sa m ple
Bl o o d sa m ple f or D N A 
p har mac o ge netics ca n be o btai ne d a n y 
ti me at or after V 2.
X
X
E n d osc o pic Pr oce d ure
E n d osc o p y
X
C CI
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
3 6
T a ble 3. Sc he d ule of A cti vities f or t he E xte nsi o n I n d ucti o n a n d E xte nsi o n M ai nte n a nce Tre at me nt Peri o ds of St u d y J 1 P- M C -K F A H
T his sc he d ule a p plies t o st u d y partici pa nts w h o are n o nr es p o n ders at Wee k 1 2.
V 1 6 pr oce d ures ma y be c o n d ucte d o ver m ore t ha n 1 da y as l o n g as all acti vities are c o m plete d wit hi n t he all o wa ble visit t olera nce a n d all sc he d ule d acti vities are 
c o m plete d pri or t o d osi n g
F or pr oce d ures at a n E T V , see E T V i n Ta ble 4. 
F or pr oce d ures at a n u ns c h e d ule d visit , see V 9 9 7 i n Ta ble 4.
Visits 1 7 t hr o u g h 2 8 are eli gi ble t o be c o n d ucte d re m otel y (t hat is, b y tele p h o ne, I T-assiste d virt ual visit, m o bile healt hcare, or a c o m bi nati o n t here of) if writte n 
a p pr o val is pr o vi de d b y t he s p o ns or a n d acc or di n g t o t he prefere nces of t he partici pa nt a n d t he st u d y site. H o we ver, n o m ore t ha n 3 4 da ys ca n ela pse wit h o ut a n 
o n -site st u d y visit occ urri n g.
Visit n u m ber
V 1 0
V 1 1
V 1 2
V 1 3
V 1 4
V 1 5
V 1 6
V 1 7
V 1 8
V 1 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
1 4
1 6
1 8
2 0
2 2
2 4
2 6
2 8
3 0
3 2
St u d y da y
9 9
1 1 3
1 2 7
1 4 1
1 5 5
1 6 9
1 8 3
1 9 7
2 1 1
2 2 5
Visit i nter val t olera nce ( d a ys)
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
C ol o n bi o ps y sa m ple c ollecti o n
X
Perf or me d at ti me of e n d osc o p y. 
Ins tr ucti ons f or c ollecti o n are pr o vi de d 
i n t he la b ma n ual. Fle xi ble 
si g m oi d osc o p y is rec o m me n de d, e xce pt 
f or pr ot oc ol-s pecifie d reas o ns w he n a 
c ol o n osc o p y s h o ul d be perf or me d.
St o ol S a m ples
X
X
X
X
R a n d o miz ati o n a n d D osi n g
D osi n g
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
3 7
T a ble 3 (c o nti n ue d). Sc he d ule of acti vities f or t he E xte nsi o n I n d ucti o n a n d E xte nsi o n M ai nte n a nce Tre at me nt Peri o ds of St u d y J 1 P- M C -K F A H
T his sc he d ule a p plies t o st u d y partici pa nts w h o are n o nr es p o n ders at Wee k 1 2.
F or pr oce d ures at a n E T V , see E T V i n Ta ble 4. 
F or pr oce d ures at a n u nsc he d ule d visit , see V 9 9 7 i n Ta ble 4.
Visits 1 7 t hr o u g h 2 8 are eli gi ble t o be c o n d ucte d re m otel y (t hat is, b y tele p h one, I T-assiste d virt ual visit, m o bile healt hcare, or a c o m bi nati o n t here of) if writte n a p pr o val 
is pr o vi de d b y t he s p o ns or a n d acc or di n g t o t he prefere nces of t he partici pa nt a n d t he st u d y site. H o we ver, n o m ore t ha n 3 4 da ys ca n ela pse wit h o ut a n o n -site st u d y visit 
occ urri n g
Visit n u m ber
V 2 0
V 2 1
V 2 2
V 2 3
V 2 4
V 2 5
V 2 6
V 2 7
V 2 8
V 2 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
3 4
3 6
3 8
4 0
4 2
4 4
4 6
4 8
5 0
5 2
St u d y da y
2 3 9
2 5 3
2 6 7
2 8 1
2 9 5
3 0 9
3 2 3
3 3 7
3 5 1
3 6 5
Visit i nter val t olera nce ( d a ys)
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
C o nc o mita nt me dicati o ns
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
A d verse e ve nts
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
F or A E SIs, a d diti o nal data are c ollecte d 
( Secti o n 8. 3. 6 ).
Re vie w m o difie d Ma y o sc ore ( M M S)
X
T o bacc o use
X
P h ysic al E v al u ati o n
Wei g ht
X
X
Vital si g ns
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Bl o o d press ure, b o d y te m perat ure, a n d p ulse 
rate. Vital si g ns s h o ul d be meas ure d after 
partici pa nt has bee n sitti n g f or at least 5 
mi n utes.
S y m pt o m -directe d p h ysical e xa mi nati o n ,
i ncl u di n g assess me nt f or si g ns a n d 
s ym pt o ms of t u berc ul osis ( T B), i ncl u di n g 
peri p heral l y m p h n o des
X
X
See Secti o n 8. 2. 2 .
X
X
1 2 -lea d electr ocar di o gra m (E C G )
X
X
L ocall y perf or me d.
C CI


CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
38
Table 3 (continued). Schedule of activities for the Extension Induction and Extension Maintenance Treatment Periods of Study J1P-MC-KFAH
This schedule applies to study participants who are nonresponders at Week 12.
For procedures at an ETV, see ETV in Table 4. 
For procedures at an unscheduled visit, see V997 in Table 4.
Visits 17 through 28 are eligible to be conducted remotely (that is, by telephone, IT-assisted virtual visit, mobile healthcare, or a combination thereof) if written approval 
is provided by the sponsor and according to the preferences of the participant and the study site. However, no more than 34 days can elapse without an on-site study visit 
occurring
Visit number
V20
V21
V22
V23
V24
V25
V26
V27
V28
V29
Comment
Weeks from randomization
34
36
38
40
42
44
46
48
50
52
Study day
239
253
267
281
295
309
323
337
351
365
Visit interval tolerance (days)
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
Fasting visit
X
Patient Diary (Electronic)
Diary compliance check
X
X
X
X
X
X
X
X
X
X
Check compliance for
  Stool Frequency
  Rectal Bleeding
  Nocturnal Stools
  Bristol Stool Scale
  Urgency NRS
  Abdominal Pain NRS
  Fatigue NRS, and
  Patient Global Rating of Severity (PGR-S).
Diary return
X
Patient-Reported Outcomes 
(Electronic)
Inflammatory Bowel Disease 
Questionnaire (IBDQ)
X
Patient Global Impression of Change 
(PGI-C)
X
QIDS-SR16
X
Clinician-Administered Questionnaires 
(Paper)
Physician’s Global Assessment (PGA)
X


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
3 9
T a ble 3 (c o nti n ue d). Sc he d ule of acti vities f or t he E xte nsi o n I n d ucti o n a n d E xte nsi o n M ai nte n a nce Tre at me nt Peri o ds of St u d y J 1 P- M C -K F A H
T his sc he d ule a p plies t o st u d y partici pa nts w h o are n o nr es p o n ders at Wee k 1 2.
F or pr oce d ures at a n E T V , see E T V i n Ta ble 4. 
F or pr oce d ures at a n u nsc he d ule d visit , see V 9 9 7 i n Ta ble 4.
Visits 1 7 t hr o u g h 2 8 are eli gi ble t o be c o n d ucte d re m otel y (t hat is, b y tele p h one, I T-assiste d virt ual visit, m o bile healt hcare, or a c o m bi nati o n t here of) if writte n a p pr o val 
is pr o vi de d b y t he s p o ns or a n d acc or di n g t o t he prefere nces of t he partici pa nt a n d t he st u d y site. H o we ver, n o m ore t ha n 3 4 da ys ca n ela pse wit h o ut a n o n -site st u d y visit 
occ urri n g
Visit n u m ber
V 2 0
V 2 1
V 2 2
V 2 3
V 2 4
V 2 5
V 2 6
V 2 7
V 2 8
V 2 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
3 4
3 6
3 8
4 0
4 2
4 4
4 6
4 8
5 0
5 2
St u d y da y
2 3 9
2 5 3
2 6 7
2 8 1
2 9 5
3 0 9
3 2 3
3 3 7
3 5 1
3 6 5
Visit i nter val t olera nce ( d a ys)
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
L a b or at or y Tests a n d S a m ple 
C ollecti o ns
He mat ol o g y
X  
X  
X
X
X
X
Cli nical c he mistr y
X  
X  
X
X
X
X
Li pi d pa nel
X
Fasti n g sa m ples are preferre d, b ut if 
partici pa nt is n onfasti n g at ti me of c ollecti o n, 
t his is n ot a pr ot oc ol de viati o n.
Ur i nal ysis
X
Ur i ne pre g na nc y (l ocal)
X
X
X
X
X
P erf or m o nl y f or w o me n of c hil d beari n g 
p ote ntial a n d w o me n wit h a hist or y of t u bal 
li gati on. At d osi n g visits w hic h ha ve 
pre g na nc y testi n g, t he pre g na nc y test res ult 
m ust be c o nfir me d t o be ne gati ve pri or t o 
d osi n g . Pr e g na nc y testi n g m a y be perf or me d 
m ore f re q ue ntl y t ha n desi g nate d o n t he So A 
if l ocal la ws or  re g ulati o ns re q uire m ore 
fre q ue nt testi n g.
X
X
H B V D N A
X
X
O nl y f or partici pa nts w h o are p ositi ve f or 
a nti ‑ H Bc at scree ni n g.
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
4 0
T a ble 3 (c o nti n ue d). Sc he d ule of acti vities f or t he E xte nsi o n I n d ucti o n a n d E xte nsi o n M ai nte n a nce Tre at me nt Peri o ds of St u d y J 1 P- M C -K F A H
T his sc he d ule a p plies t o st u d y partici pa nts w h o are n o nr es p o n ders at Wee k 1 2.
F or pr oce d ures at a n E T V , see E T V i n Ta ble 4. 
F or pr oce d ures at a n u nsc he d ule d visit , see V 9 9 7 i n Ta ble 4.
Visits 1 7 t hr o u g h 2 8 are eli gi ble t o be c o n d ucte d re m otel y (t hat is, b y tele p h one, I T-assiste d virt ual visit, m o bile healt hcare, or a c o m bi nati o n t here of) if writte n a p pr o val 
is pr o vi de d b y t he s p o ns or a n d acc or di n g t o t he prefere nces of t he partici pa nt a n d t he st u d y site. H o we ver, n o m ore t ha n 3 4 da ys ca n ela pse wit h o ut a n o n -site st u d y visit 
occ urri n g
Visit n u m ber
V 2 0
V 2 1
V 2 2
V 2 3
V 2 4
V 2 5
V 2 6
V 2 7
V 2 8
V 2 9
C o m me nt
Wee k s fr o m ra n d o mizati o n
3 4
3 6
3 8
4 0
4 2
4 4
4 6
4 8
5 0
5 2
St u d y da y
2 3 9
2 5 3
2 6 7
2 8 1
2 9 5
3 0 9
3 2 3
3 3 7
3 5 1
3 6 5
Visit i nter val t olera nce ( d a ys)
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
± 3
F asti n g visit
X
P har mac o ki netic ( P K) sa m ples
X
X
C ollect sa m ples bef ore d osi n g, if d osi n g is 
sc he d ule d. C ollect a d diti o nal sa m ples at 
s pecifie d ti mes relati ve t o o nset of 
h y perse nsiti vit y e ve nts.
X
X
C ollect sa m ples bef ore d osi n g, if d osi n g is 
sc he d ule d. C ollect a d diti o nal sa m ples at 
s pecifie d ti mes relati ve t o o nset of 
h y perse nsiti vit y e ve nts.
Fl o w c yt o metr y pa nel
X
G e netics sa m ple
Bl o o d sa m ple f or D N A p har mac o ge netics 
ca n be o btai ne d a n y ti me at or after V 2.
X
E n d osc o pic Pr oce d ure
E n d osc o p y
X
C ol o n bi o ps y sa m ple c ollecti o n
X
Perf or me d at ti me of e n d osc o p y. Instr ucti o n s
f or c ollecti o n are pr o vi de d i n t he la b ma n ual. 
Fle xi ble si g m oi d osc o p y is rec o m me n de d, 
e xce pt f or pr ot oc ol -s pecifie d reas o ns w he n a 
c ol o n osc o p y s h o ul d be perf or me d.
St o ol S a m ples
X
X
X
X
C CI
C CI
C CI


CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
41
Table 3 (continued). Schedule of activities for the Extension Induction and Extension Maintenance Treatment Periods of Study J1P-MC-KFAH
This schedule applies to study participants who are nonresponders at Week 12.
For procedures at an ETV, see ETV in Table 4. 
For procedures at an unscheduled visit, see V997 in Table 4.
Visits 17 through 28 are eligible to be conducted remotely (that is, by telephone, IT-assisted virtual visit, mobile healthcare, or a combination thereof) if written approval 
is provided by the sponsor and according to the preferences of the participant and the study site. However, no more than 34 days can elapse without an on-site study visit 
occurring
Visit number
V20
V21
V22
V23
V24
V25
V26
V27
V28
V29
Comment
Weeks from randomization
34
36
38
40
42
44
46
48
50
52
Study day
239
253
267
281
295
309
323
337
351
365
Visit interval tolerance (days)
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
Fasting visit
X
Randomization and Dosing
Dosing
X
X
X
X
X
X
X
X
X
No dosing at V29.
Abbreviations: AESIs = adverse event of special interest; anti-HBc = antibody to hepatitis B core antigen; DNA = deoxyribonucleic acid; ETV = early 
termination visit; HBV = hepatitis B virus; IT = information technology; NRS = numeric rating scale; QIDS-SR16 = 16-Item Quick Inventory of Depressive 
Symptomatology–Self Report; SoA = schedule of activities; V = visit.


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
4 2
1. 3. 4. Sc he d ule of acti v ities f or E T V , u nsc he d ule d visits, a n d P ost -Tre at me nt F oll o w -U p Peri o d
T a ble 4. Sc he d ule of A cti vities f or E arl y T er mi n ati o n, U nsc he d ule d V isits, a n d P ost-Tre at me nt F oll o w -U p Peri o d
V 8 0 2 is o nl y f or ra n d o mize d partici pa nts w h o were p ositi ve f or a nti -H Bc at scree ni n g. All ot her partici pa nts will ha ve t heir fi nal visit at V 8 0 1 or E T V .
V 9 9 7: A d diti o nal st u d y pr oce d ures ca n be perf or me d at t he discreti o n of t he i n vesti gat or.
Visit n u m ber
E T V
V 9 9 7
V 8 0 1
V 8 0 2
C o m me nt
Wee k s fr o m ra n d o mizati o n
—
—
5 8 or
E T V + 8 
wee ks 
after last 
d ose
6 6 or
E T V + 1 6
wee ks 
after last 
d ose
T he i nter vals bet wee n E T V a n d t he p ost-treat me nt f oll o w-u p 
visit(s) s ho ul d be a de q uate t o e ns ure t hat V 8 0 1 occ ur s at least 
8 wee ks si nce last d ose a n d V 8 0 2 (if a p plica ble) occ urs at least 
1 6 we e ks si nce last d ose.
St u d y da y
—
—
—
—
Visit i nter val t olera nce ( d a ys)
—
—
± 7
± 7
F asti n g visit
N o f asti n g i n t his peri o d
C o nc o mita nt me dicati o ns
X  
X  
X  
X
A d verse e ve nts
X  
X  
X  
X
F or A E SIs, a d diti o nal data are c ollecte d ( Secti o n 8. 3. 6 ).
Re vie w m o difie d Ma y o sc ore ( M M S)
X
T o bacc o use
X
P h ysic al E v al u ati o n
Wei g ht
X
X
Vital si g ns
X  
X  
X  
X
Bl o o d press ure, b o d y te m perat ure, a n d p ulse rate. Vital si g ns 
s h o ul d be meas ure d after partici pa nt has bee n sitti n g f or at least 
5 mi n utes.
V 9 9 7: Vital si g n s c ollecti o n is o pti o nal .
S y m pt o m -directe d p h ysical e xa mi nati o n , i ncl u di n g 
assess me nt f or si g ns a n d s y m pt o ms of t u berc ul osis 
( T B), i ncl u di n g peri p heral l y m p h n o des
X
X  
X
See Secti o n 8. 2. 2 .
X
X  
X
1 2 -lea d electr ocar di o gra m (E C G )
X
L ocall y perf or me d. 
P atie nt Di ar y ( Electr o nic)
Diar y  ret ur n
X
P atie nt -Re p orte d O utc o mes ( Electr o nic)
I nfla m mat or y B o wel Disease Q uesti o n naire (I B D Q)
X
Patie nt Gl o bal I m pressi o n of C ha n ge ( P GI -C)
X
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
4 3
T a ble 4. Sc he d ule of A cti vities f or E arl y T er mi n ati o n, U nsc he d ule d V isits, a n d P ost-Tre at me nt F oll o w -U p Peri o d
V 8 0 2 is o nl y f or ra n d o mize d partici pa nts w h o were p ositi ve f or a nti -H Bc at scree ni n g. All ot her partici pa nts will ha ve t heir fi nal visit at V 8 0 1 or E T V .
V 9 9 7: A d diti o nal st u d y pr oce d ures ca n be perf or me d at t he discreti o n of t he i n vesti gat or.
Visit n u m ber
E T V
V 9 9 7
V 8 0 1
V 8 0 2
C o m me nt
Wee k s fr o m ra n d o mizati o n
—
—
5 8 or
E T V + 8 
wee ks 
after last 
d ose
6 6 or
E T V + 1 6
wee ks 
after last 
d ose
T he i nter vals bet wee n E T V a n d t he p ost-treat me nt f oll o w-u p 
visit(s) s ho ul d be a de q uate t o e ns ure t hat V 8 0 1 occ ur s at least 
8 wee ks si nce last d ose a n d V 8 0 2 (if a p plica ble) occ urs at least 
1 6 we e ks si nce last d ose.
St u d y da y
—
—
—
—
Visit i nter val t olera nce ( d a ys)
—
—
± 7
± 7
F asti n g visit
N o f asti n g i n t his peri o d
QI D S -S R 1 6
X
Cli nici a n- A d mi nistere d Q uesti o n n aires ( P a per )
P h y sicia n’s Gl o bal Assess me nt ( P G A)
X
L a b or at or y Tests a n d S a m ple C ollecti o ns
He mat ol o g y
X
X  
X
Cli nical c he mistr y
X
X  
X
Li pi d pa nel
X
Fasti n g is n ot re q uire d f or t he li pi d pa nel at E T V .
Ur i nal ysis
X
X  
X
Ur i ne pre g na nc y (l ocal)
X
X  
X
P erf or m o nl y f or w o me n of c hil d beari n g p ote ntial a n d w o me n 
wit h a hist or y of t u bal li gati o n. At d osi n g visits w hic h ha ve 
pre g na nc y testi n g, t he pre g na nc y test res ult m ust be c o nfir me d 
t o be ne gati ve pri or t o d osi n g . Pr e g na nc y testi n g m a y be 
perf or me d m ore fre q ue nt l y t ha n desi g nate d o n t he So A if l ocal 
l a ws or  re g ulati o ns re q uire m ore fre q ue nt testi n g.
X
H B V D N A
X
X
O nl y f or partici pa nts w h o are p ositi ve f or a nti ‑ H Bc at scree ni n g.
P har mac o ki netic ( P K) sa m ples
X
X
C ollect sa m ples bef ore d osi n g, if d osi n g is sc he d ule d. C ollect 
a d diti o nal sa m ples at s pecifie d ti mes relati ve t o o nset of 
h y perse nsiti vit y e ve nts.
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
4 4
T a ble 4. Sc he d ule of A cti vities f or E arl y T er mi n ati o n, U nsc he d ule d V isits, a n d P ost-Tre at me nt F oll o w -U p Peri o d
V 8 0 2 is o nl y f or ra n d o mize d partici pa nts w h o were p ositi ve f or a nti -H Bc at scree ni n g. All ot her partici pa nts will ha ve t heir fi nal visit at V 8 0 1 or E T V .
V 9 9 7: A d diti o nal st u d y pr oce d ures ca n be perf or me d at t he discreti o n of t he i n vesti gat or.
Visit n u m ber
E T V
V 9 9 7
V 8 0 1
V 8 0 2
C o m me nt
Wee k s fr o m ra n d o mizati o n
—
—
5 8 or
E T V + 8 
wee ks 
after last 
d ose
6 6 or
E T V + 1 6
wee ks 
after last 
d ose
T he i nter vals bet wee n E T V a n d t he p ost-treat me nt f oll o w-u p 
visit(s) s ho ul d be a de q uate t o e ns ure t hat V 8 0 1 occ ur s at least 
8 wee ks si nce last d ose a n d V 8 0 2 (if a p plica ble) occ urs at least 
1 6 we e ks si nce last d ose.
St u d y da y
—
—
—
—
Visit i nter val t olera nce ( d a ys)
—
—
± 7
± 7
F asti n g visit
N o f asti n g i n t his peri o d
X
X
C ollect sa m ples bef ore d osi n g, if d osi n g is sc he d ule d. C ollect 
a d diti o nal sa m ples at s pecifie d ti mes relati ve t o o nset of 
h y perse nsiti vit y e ve nts.
Fl o w c yt o metr y pa nel
X
G e netics sa m ple
Bl o o d sa m ple f or D N A p har mac o ge netics ca n be o btai ne d a n y 
ti me at or after V 2.
X
E n d osc o pic Pr oce d ure
E n d osc o p y
X
Rec o m me n de d at E T V base d o n j u d g me nt of t he i n vesti gat or 
a n d after disc ussi o n wit h t he s p o ns or’s me dical m o nit or. If n ot 
perf or me d at E T V, t his will n ot be c o nsi dere d a pr ot oc ol 
de viati o n.
C ol o n bi o ps y sa m ple c ollecti o n
X
Rec o m me n de d at E T V base d o n j u d g me nt of t he i n vesti gat or 
a n d after disc ussi o n wit h t he s p o ns or’s me dical m o nit or. 
Ins tr ucti ons f or c ollecti o n are pr o vi de d i n t he la b ma n ual. 
Fle xi ble si g m oi d osc o p y is rec o m me n de d, e xce pt f or 
pr ot oc ol -s pecifie d reas o ns w he n a c ol o n osc o p y s h o ul d be 
perf or me d. If n ot perf or me d at E T V, t his will n ot be c o nsi dere d 
a pr ot oc ol de viati o n.
St o ol S a m ples
X
X
C CI
C CI
C CI


CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
45
Table 4. Schedule of Activities for Early Termination, Unscheduled Visits, and Post-Treatment Follow-Up Period
V802 is only for randomized participants who were positive for anti-HBc at screening. All other participants will have their final visit at V801 or ETV.
V997: Additional study procedures can be performed at the discretion of the investigator.
Visit number
ETV
V997
V801
V802
Comment
Weeks from randomization
—
—
58 or
ETV + 8 
weeks 
after last 
dose
66 or
ETV + 16
weeks 
after last 
dose
The intervals between ETV and the post-treatment follow-up 
visit(s) should be adequate to ensure that V801 occurs at least 
8 weeks since last dose and V802 (if applicable) occurs at least 
16 weeks since last dose.
Study day
—
—
—
—
Visit interval tolerance (days)
—
—
±7
±7
Fasting visit
No fasting in this period
Randomization and Dosing
Dosing
No dosing at ETV, V997, or post-treatment follow-up visits.
Abbreviations: AESIs = adverse event of special interest; anti-HBc = antibody to hepatitis B core antigen; DNA = deoxyribonucleic acid; ETV = early 
termination visit; HBV = hepatitis B virus; QIDS-SR16 = 16-Item Quick Inventory of Depressive Symptomatology–Self Report; SoA = schedule of activities; 
V = visit.


CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
46
2. Introduction
2.1. Study Rationale
LY3471851 (also known as NKTR-358) is a polyethylene glycol (PEG)-conjugated recombinant 
human interleukin (IL)-2 (rhIL-2) with the capacity to promote the expansion and activation of 
regulatory T cells (Tregs) with relatively minimal effect on conventional T cells (Tcons). In 
preliminary clinical studies, other IL-2 formulations (aldesleukin and ILT-101), which are 
hypothesized to have a mechanism of action similar to that of LY3471851, were associated with 
an expansion of peripheral Tregs and biological response in patients with UC.1,2 As compared to 
those formulations, PEGylation results in prolonged systemic exposure and improved binding to 
the high-affinity IL-2 receptor most present on Tregs.
Study KFAH is a Phase 2 study to evaluate the efficacy and safety of multiple dose levels of 
LY3471851 in adult patients with moderately to severely active UC who have an inadequate 
response to, loss of response to, or are intolerant to conventional UC therapy ("conventional-
failed") or to advanced UC therapy ("advanced therapy-failed"). For this study, conventional UC 
therapy is defined as corticosteroids, AZA, or 6-MP. Results of this study will be used to guide 
the dose selection for future studies and to further characterize the benefit/risk profile of 
LY3471851.
2.2. Background
Ulcerative colitis is a chronic disease characterized by inflammation of the rectum and colon. 
Symptoms include diarrhea, rectal bleeding (RB), urgency, and a feeling of incomplete 
evacuation of the rectum after defecation (tenesmus). Ulcerative colitis has a relapsing–remitting 
course, meaning that many patients have intermittent disease flares that are interspersed with 
periods of remission. Treatment goals in UC include induction of remission, typically within a 
6 to 12-week time frame, and maintenance of remission in the longer term, which may be over 
52 weeks of continuous treatment in clinical trials. In both clinical practice and in clinical trials, 
clinical response and clinical remission are assessed by a combination of endoscopy 
(improvement in the endoscopic appearance of the mucosa and healing of ulcers) and by patient-
reported outcomes, including reduced stool frequency (SF) and resolved RB.3 Control of 
intestinal inflammation in UC is associated with a reduction in the risk of hospitalization and 
colectomy, and in the longer term, reduction in the risk of UC-associated dysplasia and 
colorectal cancer.
Medications used for the treatment of UC include 5-ASA–containing medications (sulfasalazine, 
mesalazine, balsalazide, and olsalazine), corticosteroids, immunomodulators such as AZA and 
6-MP, biologic medications, and JAK inhibitor medications. A significant proportion of patients 
with moderately to severely active UC may 

have an inadequate response to medicines such as 5-ASAs or corticosteroids

be unable to maintain a clinical response to 5-ASAs or AZA, or

be unable to discontinue corticosteroids without a relapse in disease activity.4


CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
47
Many of these patients require additional treatment with the next line of therapy, which could 
include medical treatment with a biologic or JAK inhibitor medication or surgical treatment with 
a colectomy.
Advanced therapies, including anti-TNF antibodies (for example, infliximab, adalimumab, and 
golimumab), IL-12/23 antibodies (for example, ustekinumab), and anti-integrin antibodies (for 
example, vedolizumab), as well as tofacitinib, a JAK inhibitor, are indicated for the treatment of 
moderately to severely active UC in individuals who fail to respond to, have an inadequate 
response to, or are intolerant to 5-ASAs and immunomodulators. The key registration trials for 
the above advanced therapies show that although many participants benefitted, many also failed 
to achieve the treatment goals of clinical remission5,6. Long-term (52 weeks) clinical remission 
was achieved in less than 50% of participants.7-9,28-30. These results show that, despite an 
improving treatment landscape, a sizable proportion of individuals do not respond to available 
treatments, underscoring the need for new therapeutic options for individuals with moderately to 
severely active UC.
Dysfunction in Treg cell biology has been proposed as a factor in the pathophysiology of 
UC.10,11 The goal of LY3471851 therapy is to increase Treg number and function, with a 
minimal effect on Tcons and NK cells.
2.3. Benefit/Risk Assessment
The Investigator's Brochure (IB) designates local injection site reactions as an identified risk of 
LY3471851, based on reports of primarily low-grade injection site reactions in the Phase 1 
studies. Reports of cytokine release syndrome and clinical symptom complex attributed to 
elevated cytokine levels were of Grade 1 severity. Eosinophilia without evidence of target organ 
damage was observed in some participants in the Phase 1 study involving patients with systemic 
lupus erythematosus (SLE). The safety findings from Phase 1 studies showed no evidence of 
AEs characteristic of capillary leak syndrome, increased risk of infection, worsening or new 
onset autoimmune disease, cardiac disorders (cardiac rhythm disturbances, angina, or myocardial 
infarction), pulmonary disorders, central nervous system effects, or severe 
anemia/thrombocytopenia known to be associated with high-dose IL 2 (aldesleukin).
To minimize risks to participants in Study KFAH, enrolled participants will have appropriate 
predose safety assessments and post-dose monitoring. The routine safety assessments include 
physical examinations, clinical safety laboratory tests (including hematology and chemistry), 
suicidality/self-harm and depression evaluations, and collection of vital signs and spontaneously 
reported AEs. The study design includes a post-treatment follow-up period with at least one visit 
for safety assessments.
Systemic allergic/hypersensitivity reactions, which include anaphylaxis12 and other immediate 
allergic type reactions, such as non-antibody mediated systemic reactions (for example, cytokine 
release syndrome [CRS]), are among the study’s AESIs (see Section 8.3.6.1). These reactions, if 
they occur, will prompt additional testing and data collection, and are among the reasons that a 
participant might be discontinued from study drug (Section 7.1.1). Other AESIs, for example, 
infections, are likewise addressed by special data collection and other considerations of this 
protocol (Section 8.3.6.2).


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Protocol J1P-MC-KFAH(b)
48
In addition, based on observations of treatment-related biliary hyperplasia noted in nonclinical 
studies, as described in the IB, investigators should be aware of the possible occurrence of 
treatment-related hepatobiliary changes that could possibly include cholestasis. The protocol 
includes hepatic-related laboratory testing to support intensive monitoring for symptoms and 
physical signs suggestive of liver or biliary toxicity, including jaundice, scleral icterus, and 
pruritis (see Section 8.2.9).
Ongoing study-level monitoring of safety data will be performed, as described in Section 8.2. 
Interim analyses to review unblinded safety data will also be conducted, as described in 
Section 9.5 and Section 10.1.5.
The efficacy of LY3471851 in UC has not been established. Participants may benefit by 
receiving personal health information from the physical examinations and from other routine 
safety assessments performed in this study.
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of LY3471851 may be found in the IB.


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Protocol J1P-MC-KFAH(b)
49
3. Objectives and Endpoints
This table shows the objectives, endpoints, and estimands of the study. Primary and secondary 
efficacy endpoint definitions appear in Section 8.1.
Objectives
Estimands/Endpoints
Primary

To determine whether LY3471851 is superior 
to placebo in inducing clinical remission in 
participants with moderately to severely 
active UC
The study will compare LY3471851 with placebo in 
participants with moderately to severely active UC.
The primary comparison of interest is the difference in the 
proportion of participants who achieve clinical remission
at Week 12.
The primary comparison will be assessed using a 
composite estimand where the intercurrent events that lead 
to permanent discontinuation of assigned study treatment 
are part of the response definition.
Secondary

To evaluate the efficacy of induction 
treatment with LY3471851 compared to 
placebo with respect to clinical, endoscopic,
and histologic improvement
Secondary comparisons of interest are the difference 
between LY3471851 and placebo in the proportion of 
participants who have not permanently discontinued at 
Week 12 and have achieved at Week 12: 

clinical response

endoscopic remission

endoscopic response

symptomatic remission

symptomatic response

histologic remission

histologic-endoscopic mucosal healing
Secondary comparisons with binary endpoints will use a 
composite estimand as described for the primary 
comparison.


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
5 0
O bjecti ves
Esti m a n ds/ E n d p oi nts

T o e val uate t he efficac y of mai nte na nce 
treat me nt wit h L Y 3 4 7 1 8 5 1 c o m pare d t o 
place b o wit h res pect t o cli nical, e n d osc o pic,
a n d hist ol o gic i m pr o ve me nt
Sec o n dar y c o m paris o ns of i nterest i ncl u de t he differe nce 
bet wee n L Y 3 4 7 1 8 5 1 a n d place b o i n t he pr o p orti o n of 
partici pa nts w h o were res p o n ders at Wee k
1 2 ( Wee k 1 2 
Res p o n ders) a n d ha ve n ot per ma ne ntl y disc o nti n ue d at 
Wee k 5 2, w h o at Wee k 5 2
still ha ve 

cli nical re missi o n

cli nical res p o nse 

e n d osc o pic re missi o n

e n d osc o pic res p o nse

s ym pt o matic re missi o n

s ym pt o matic res p o nse

hist ol o gic re missi o n

hist ol o gic -e n d osc o pic m uc osal heali n g
Sec o n dar y c o m paris o ns wit h bi nar y e n d p oi nts will use a 
c o m p osite esti ma n d as descri be d f or t he pri mar y 
c o m paris o n .

T o e val uate t he efficac y of treat me nt wit h 
L Y 3 4 7 1 8 5 1 c o m pare d t o place b o wit h 
res pect t o patie nt-re p orte d o utc o mes a n d 
q ualit y  of life meas ures
C o m paris o n of m ea n c h a n ges fr o m baseli ne t o Wee k 1 2 
a n d t o Wee k 5 2 i n sc ores f or

I B D Q

Ur ge nc y N R S

A b d o mi nal Pai n N R S

N oct ur n al St o ols

Br ist ol St o ol Scale

P G R - S

F ati g ue N R S
Sec o n dar y c o m paris o ns wit h c o nti n u o us e n d p oi nts will 
use a h y p ot hetical efficac y esti ma n d strate g y t o a d dress 
t he i nterc urre nt e ve nts of earl y disc o nti n uati o n t o assess 
t he effect of st u d y treat me nt i n a h y p ot hetical trial w here 
all partici pa nts ha ve c o m plete data a n d c o nti n ue t o ta ke 
st u d y treat me nt wit h o ut disc o nti n ui n g fr o m t he st u d y.

T o e val uate t he P K of L Y 3 4 7 1 8 5 1

Wee k 1 2 L Y 3 4 7 1 8 5 1 tr o u g h c o nce ntrati o ns
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
5 1
O bjecti ves
Esti m a n ds/ E n d p oi nts
A b bre viati o ns:
I B D Q = I nfla m mat or y B o wel Disease Q uesti o n naire; N R S = 
n u meric rati n g scale; P G R -S = Patie nt’s Gl o bal R ati n g of Se verit y; P K = p har mac o ki netics; U C – ulcerati ve 
c olitis;
A d dit i onal details will be pr o vi de d i n t he S A P.
C CI
C CIC CI


CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
52
4. Study Design
4.1. Overall Design
Study KFAH is an adaptive Phase 2 multicenter, randomized, double-blind, placebo-controlled, 
parallel-group study to evaluate the efficacy and safety of multiple dose levels of LY3471851 in 
adult patients with moderately to severely active UC. Enrolled study participants will have either

an inadequate response to, loss of response to, or be intolerant to corticosteroid or 
immunomodulator therapy for UC (termed “conventional-failed” in this protocol), or

an inadequate response to, loss of response to, or are intolerant to biologic or JAK 
inhibitor therapy for UC (termed “advanced therapy-failed” in this protocol).
For complete definitions of the terms “conventional-failed” and “advanced therapy-failed,” see 
the study entry criteria listed in Section 5.1.
Study Stages
This adaptive study has two stages, as shown in the lower left of the first schema in Section 1.2.
Stage 1:
A prespecified number of study participants will be randomly assigned to one of 
three treatment groups, including placebo. Interim analyses will be conducted for 
safety, dosing tolerability, and efficacy. These interim analyses will determine the 
doses to be used in Stage 2.
Note: Participants enrolled during Stage 1 of the study will remain on their 
randomly assigned Stage 1 doses. Their doses will be changed only if necessary 
due to safety reasons or due to their clinical response status.
Stage 2:
A prespecified number of additional study participants will be enrolled and 
randomly assigned to study treatment groups as well as placebo. The treatment 
doses used in Stage 2 may include any of the doses used in Stage 1 (or none), as 
well as one or more additional LY3471851 doses, not exceeding1800 µg. The 
Stage 2 LY3471851 treatment doses will be determined by the sponsor based on 
results of the Stage 1 interim analyses and recommendations of the sponsor’s 
IAC. For example, a small group of sponsor personnel having pre-identified roles 
and no contact with investigative sites may review the IAC recommendation and 
may also review unblinded data in order to further assess the recommendation. 
Details regarding the process for internal decision-making and action plan will be 
provided in a separate document.
Thus, whereas Stage 1 will have three treatment groups (including placebo), Stage 2 could have
more treatment groups or fewer.
The sponsor intends for the transition from Stage 1 to Stage 2 to be seamless, with participant
screening and enrollment activities occurring continuously in the transition period. The study 
IWRS will allocate newly enrolling participants to groups according to the Stage 1 
randomization ratio until the Stage 2 groups have been decided upon and implemented.
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St u d y P eri o ds
T his st u d y  has mul tiple peri o ds, as s h o w n t he sc he ma i n Secti on 1. 2 . 
Scree ni n g p erio d
T his p eri o d be gi ns wit h Visit 1, w hic h occ urs 5 wee ks ( or less) bef ore t he pla n ne d ra n d o mizati o n 
visit. A partici pa nt’s scree ni n g e val uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t he 
parti ci pa nt’s eli gi bilit y bef ore ra n d o mizat i on a n d d osi n g occ urs at Visit 2.
Bli n de d in d uct i on a n d b li n de d m ai nte na nce p erio ds
T he d o u bl e- bli n d, pl ace b o -c o ntr olle d, 1 2- wee k i n d ucti o n treatme nt  perio d be gi ns at Visit 2. 
D osi n g , sa m ple c ollecti on, a n d assess me nts c o ntin ue Q 2 W , as s h o w n i n t he S O A. Bet wee n 
Wee k 1 2 a n d Wee k 1 4, b ase d o n sa m ples a n d assess me nts c ollecte d at Wee k
1 2, parti ci pa nts 
will be classifie d as eit h er “Wee k 1 2 Res p o n ders ” or “Wee k
1 2 N o nres p o n ders ” base d o n t he 
“cli nical res p o nse” criteria defi ne d i n Sect i on 8. 1 .

“Wee k 1 2 Res p o n ders ” will c o nt i n ue t o recei ve t heir sa me ra n d oml y assi g ne d treat me nt 
t hr o u g ho ut t he bli n de d 4 0- wee k Mai nte na nce Peri o d , wit h t he fi nal d ose occ urri n g at 
Wee k
5 0 a n d t he last mai nte na nce assess me nts a n d sa m ple c ollecti ons at Wee k 5 2.

“Wee k 1 2 N o nres p o n ders ” will e nter t he E xte nsi o n I n d uc tio n a n d E xte nsi o n Mai nte na nce 
P eri o ds.
E xte nsi o n in d ucti o n a n d m ai nte na nce p erio ds
Be gi n ni n g at Wee k 1 4, partici pa nts w h o were classi fie d as Wee k 1 2 N o nres p o n ders will recei ve 
the hi g h d ose (
 µ g) of L Y 3 4 7 1 8 5 1 Q 2 W, u nless a lo wer d ose is selecte d f or Sta ge 2 base d 
o n i nteri m a nal yses .
Bet wee n Wee k 2 6 a n d Wee k 2 8, base d o n sa m ples a n d assess me nts c ollecte d at Wee k 2 6, t hese 
parti ci pa nts will a gai n be classifie d acc or di n g t o t heir res p o nse status (res p o n der or 
n o nres p o n der) .

P arti cipa nts w h o are cl assifie d as res p o n ders base d o n t he sa mpl e s a n d assess me nts at 
Wee k 2 6 will c o nt i n ue t o recei ve L Y 3 4 7 1 8 5 1 Q 2 W as mai nte na nce t hr o u g h t he 
r e mai n der of t he st u d y. T hese partici pa nts ha ve t heir fi nal d ose at Wee k 5 0 a n d t he ir last 
mai nte na nce assess me nts a n d sa m ple c o llecti ons at Wee k 5 2 . 

P arti cipa nts w h o are cl assifie d as n o nres p o n ders base d o n t he Wee k 2 6 sa m ples a n d 
assess me nts will be per ma ne nt l y disc o nti n ue d fr o m st u d y dr u g w he n his/ her stat us as a 
n o nres p o n der has bee n deter mi ne d ; s uc h partici pa nts will e nter t he p ost -treat me nt 
f oll ow- u p peri o d (Secti o n 7. 1. 1 ).
P os t-treat me nt fol l ow- u p peri o d
All partici pa nts will ha ve a p ost -treat me nt fol l ow- u p visit ( Visit 8 0 1) f or safet y assess me nts. 
Vi sit 8 0 1 occ urs a p pr o xi matel y 6 wee ks after t he Wee k 5 2 visit. T he last d ose of st u d y  dr u g is 
gi ve n at Wee k 5 0. T h us, partici pa nts will ha ve bee n wit h dra w n fr o m st u d y dr u g f or 
a p pr o xi matel y 8 wee ks at Visit 8 0 1. P artici pa nts w h o were p osit i ve f or a nti-H Bc at scree ni n g 
will ha ve o ne a d dit i onal p ost -treat me nt f oll ow- u p visit ( Visit 8 0 2).
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Early discontinuation
Participants who permanently discontinue the study drug early or withdraw from the study 
(Section 7) will undergo early termination procedures, including an ETV and the post-treatment 
follow-up visits specified in the SoA.
4.2. Scientific Rationale for Study Design
Primary endpoint definition
The primary endpoint for this study tests the superiority of treatment with LY3471851 versus 
placebo for clinical remission at Week 12. The endpoint of the MMS was chosen based on 
available regulatory guidance from the 2016 FDA “Guidance for industry. Ulcerative colitis: 
clinical trial endpoints” and the 2018 EMA “Guideline on the development of new medicinal 
products for the treatment of UC.” 14,31 Both recommend a composite endpoint for both 
symptomatic and endoscopic remission. The timing of the primary endpoint was based on the 
PK/PD results of LY3471851 in the Phase 1 single- and multiple-ascending dose studies.
Duration of treatment periods and post-treatment follow-up
The 52-week total duration of treatment was chosen based on the 2018 EMA guideline14, which 
recommends at least 12 months for the assessment of long-term efficacy of maintenance of 
remission.
The post-treatment follow-up period allows for continued safety monitoring after the last dose. A 
period of 6 weeks for the post-treatment follow-up is considered sufficient to wash out study 
drug based on the mean half-life, which has been estimated as between 8 to 13 days in the 
Phase 1 studies.
The inclusion of an extension period for participants who were not clinical responders after the 
first 12 weeks of treatment is intended to provide additional time for participants on the highest 
dose to receive potential benefit and respond, and also for participants receiving the lower doses 
and placebo the opportunity to receive potential benefit and respond to the highest dose.
Choice of control and number of treatment groups
The double-blind, placebo-controlled design of this study limits potential bias in investigator 
assessments and enables a clearer interpretation of the effects of active drug compared to placebo 
(background therapy). Nonbiologic background therapy, such as 5-ASA, corticosteroids, AZA, 
or 6-MP, is allowed in this study with limitations as described in the dose stabilization criteria 
and listing of allowed concomitant medications. The selection of placebo as a comparator for this 
study is warranted because study participants will be permitted to use these medications as 
background therapy.13,14
The use of multiple active dose levels in this study will allow for an evaluation of safety and 
efficacy across a broad dose range and so provide information to guide dose selection for future 
studies.
Demographics collection
In this study, collection of demographic information includes race and ethnicity. The scientific 
rationale is based on the possible need to assess variable response in safety and/or efficacy based 
on race or ethnicity. Such a need can be addressed only if all the relevant data are collected.


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E xcl usi o n of certai n st u d y  ca n di dates
Male a n d fe male partici pa nts fr o m 1 8 t o 7 5 years of a ge , i nclusi ve, at scree ni n g will be i ncl u de d 
i n t his st u d y. Elderl y  patien ts are at i ncrease d ris k of isc he mic c olitis a n d se g me ntal c olitis 
ass ociat e d wit h di vertic ula, w hic h ma y c o nf o u n d efficac y assess me nt. Elderl y  patient s are als o at 
i ncrease d ris k of h os pitalizati on a n d p o orer o utc o mes f o ll owi n g h os pi talizati on f or U C, w hic h 
i ncl u de a n i ncrease d ris k of ve n o us t hr o m b oe m b olis m a n d m ortality.  Elderl y  p atie nts w h o 
re q uire s ur ger y for U C als o ha ve i ncrease d rates of p ost o perati ve c o m plicati o ns a n d i ncrease d 
le n gt h of h os pital sta y c o mp ar e d wi t h yo u n ger patie nts. 1 5
4. 2. 1. P artici p a nt I n p ut i nt o Desi g n
T he s p o ns or has i n v o l ve d i n vesti gati ve sites a n d patie nts i n e ve nts s oliciti n g i n p ut o n t he st u d y 
desi g n a n d i m ple me ntati o n o f pri or U C cli nical de vel o p me nt pr o gra ms. T he st u d y 
i m ple me ntati o n i nsi g hts gai ne d fr o m t h ose e ve nts were c o nsi dere d i n t he desi g n of t his st u d y.
4. 3. J ustific ati o n f or D ose
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4. 4. E n d of St u d y Defi niti o n
A partici pa nt is c o nsi dere d t o ha ve c o m p lete d t he st u d y if he or s he has c o m p lete d all re q uire d 
p eri o ds of  t he st u d y, i ncl u di n g t he last visit or t he last sc he d ule d pr oce d ure s h o w n i n t he S o A.
T he “e n d of t he st u d y” is defi ne d as t he date of t he last visit or last sc he d ule d pr oce d ure s h o w n 
i n t he S o A f or t he last partici pa nt i n t he st u d y glo b all y .
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5. Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted.
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria.
The investigator will maintain a screening log to record details of all participants screened and to 
confirm eligibility or record reasons for screening failure, as applicable.
For rescreening and retesting activities within the screening period, see Section 5.4.
5.1. Inclusion Criteria
Patients with UC will be included in the study only if they meet all of the following inclusion 
criteria.
Informed Consent
1.
Are capable of giving informed consent as described in Appendix 1, Section 10.1.3,
which includes compliance with the requirements and restrictions listed in the ICF and 
in this protocol, including the contraception requirements.
Note: For the contraception requirements of this protocol, see Appendix 4. 
Contraceptive use by men or women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies.
Patient Characteristics
2.
Are male or female patients from 18 to 75 years of age, inclusive, at the time of initial 
screening (Visit 1).
Note: Women of child-bearing potential (WOCBP) must test negative for pregnancy as 
indicated by a negative serum pregnancy test at the screening visit followed by a 
negative urine pregnancy test within 24 hours prior to first exposure to study drug.
3.
Have venous access sufficient to allow the protocol-required blood sampling.
4.
Are willing and able to complete the scheduled study assessments, including 
endoscopies and daily diary entries.
Disease-Specific Characteristics
5.
Have had an established diagnosis of UC of ≥3 months in duration before baseline 
(Visit 2), which includes endoscopic evidence of UC and a histopathology report that 
supports a diagnosis of UC (see Section 8.1.1.3). Supportive endoscopy and 
histopathology reports must be available in the source documents.
6.
Have moderately to severely active UC as defined by a modified Mayo score (MMS) of 
4 to 9 with an endoscopic subscore (ES) ≥2, with endoscopy performed within 14 days 
before baseline.
Note: The MMS requires accurate documentation of the stool frequency (i.e. baseline 
prior to onset of UC signs/symptoms OR stool frequency when in remission) as well as 


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3 days of diary data (of stool frequency and rectal bleeding) in the 7 days preceding the 
first date of bowel prep, if no bowel prep, day of endoscopy).
Note: The Mayo ES, as determined by the Image Review charter, will be provided to 
the site prior to randomization to enable determination of the MMS for eligibility.
7.
Have evidence of UC extending proximal to the rectum (with ≥15 cm of involved 
colon).
8.
Have documentation of
8a.
a surveillance colonoscopy (performed according to local standard) within 12 months 
before baseline for

patients with pancolitis of greater than 8 years’ duration, or

patients with left-sided colitis of greater than 12 years’ duration, or

patients with primary sclerosing cholangitis.
OR
8b.
in patients for whom Inclusion Criterion 8a does not apply, up-to-date colorectal cancer 
surveillance (performed according to local standard).
Note: At the discretion of the investigator, a colonoscopy instead of a flexible 
sigmoidoscopy can be performed as the screening endoscopy for this study. Patients 
who do not have a colonoscopy report available in source documentation will have a 
colonoscopy at screening.
Prior Medication Failure
9.
Have an inadequate response to, loss of response to, or intolerance to at least 1 of the 
medications described in Inclusion Criteria 9a OR 9b. Documentation of dose, 
frequency, route of administration, and duration of the prior failed treatment is required.
9a.
Conventional-failed patients: Patients who have an inadequate response to, loss of 
response to, or are intolerant to at least 1 of the following medications:

corticosteroids
o
corticosteroid-refractory colitis, defined as signs and/or symptoms of active 
UC despite oral prednisone (or equivalent oral corticosteroid) at doses of at 
least 30 mg/day for a minimum of 2 weeks; or
o
corticosteroid-dependent colitis, defined as:

an inability to reduce corticosteroids below the equivalent of 
prednisone 10 mg/day within 3 months of starting corticosteroids 
without a return of signs and/or symptoms of active UC; or

a relapse within 3 months of completing a course of corticosteroids; 
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o
history of intolerance of corticosteroids (including, but not limited to, 
Cushing’s syndrome, osteopenia/osteoporosis, hyperglycemia, or 
neuropsychiatric side-effects, including insomnia, associated with 
corticosteroid treatment).

immunomodulators
o
signs and/or symptoms of persistently active disease despite at least 
3 months’ treatment with one of the following:

oral AZA (≥1.5 mg/kg/day) or 6-MP (≥0.75 mg/kg/day), or

oral AZA or 6-MP within a therapeutic range as judged by 
thioguanine metabolite testing, or

a combination of a thiopurine and allopurinol within a therapeutic 
range as judged by thioguanine metabolite testing
o
history of intolerance to at least 1 immunomodulator; intolerance includes, 
but not limited to, nausea/vomiting, abdominal pain, pancreatitis, liver 
function test abnormalities, and lymphopenia
AND

have neither failed nor demonstrated an intolerance to an advanced therapy 
(biologic medication such as anti-TNF, anti-IL12p40 or anti-integrin antibody or a 
JAK inhibitor) indicated for the treatment of UC 
o
Participants without any prior exposure to these treatments would meet this 
part of this criterion.
o
Participants with prior exposure to these treatments could meet part of this 
criterion if the treatment duration was 1 year or less and the treatment was 
discontinued for reasons other than loss of response, inadequate response, or 
intolerance (for example, change of insurance or well-controlled disease).
9b.
Advanced therapy-failed patients: Patients who have an inadequate response to, loss 
of response to, or are intolerant to advanced therapy for UC, defined as anti-TNF 
antibodies, anti-IL12p40 antibodies or anti-integrin antibodies, or JAK inhibitors, such 
as tofacitinib. The medication used to qualify the patient for entry into this category 
must be approved for the treatment of UC in the United States, European Union, or 
Japan. Investigators must be able to document an adequate clinical trial of the 
medication. Patients should fulfill 1 of the following criteria:

Inadequate response: Signs and symptoms of persistently active disease despite 
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
Loss of response: Recurrence of signs and symptoms of active disease during 
approved maintenance dosing following prior clinical benefit (discontinuation 
despite clinical benefit does not qualify as having failed or being intolerant to UC 
advanced therapy), or

Intolerance: History of intolerance to infliximab, adalimumab, golimumab, 
ustekinumab, vedolizumab, tofacitinib, or other approved biologics or JAK 
inhibitors including, but not limited to, infusion-related event, demyelination, 
congestive heart failure, or any other drug-related AE that led to a reduction in dose 
or discontinuation of the medication.
Patients previously exposed to advanced therapy who do not meet Inclusion Criterion 
9b must still meet Inclusion Criterion 9a in order to be eligible to participate in the 
study.
Patients previously exposed to investigational therapies for the treatment of UC must 
still meet Inclusion Criteria 9a OR 9b.
Patients who meet both Inclusion Criteria 9a and 9b will be considered to be “advanced 
therapy-failed” for the purpose of this study.
Ulcerative Colitis Medication Dose Stabilization
10.
Are on a stable dose, defined as listed here, if using these medications:
10a. oral 5-ASA therapy: The prescribed dose has been stable for at least 2 weeks prior to 
the screening endoscopy.
10b. oral corticosteroid therapy (prednisone ≤20 mg/day or equivalent, or budesonide 
extended release tablets 9 mg/day [budesonide MMX]): The prescribed dose has been 
stable for at least 2 weeks before the screening endoscopy.
10c. AZA, 6-MP, and methotrexate: The prescribed dose has been stable for at least 8 weeks 
before the screening endoscopy.
Diagnostic Assessments
11.
Have clinically acceptable central laboratory test results at screening (retesting is 
allowed for hematology and chemistry), as assessed by the investigator, including
11a. hematology

absolute neutrophil count ≥1.5 times (x) 109/L (≥1.5x103/μL or ≥1.5 GI/L)

platelet count ≥100x109/L (≥100x103/μL or ≥100 GI/L)

hemoglobin ≥8.5 g/dL (≥85 g/L) for males and >8.0 g/dL (>80 g/L) for females

lymphocyte count ≥500 cells/μL (>0.50x103/μL or >0.50 GI/L), and

total white blood cell count ≥3.0x109/L (≥3.0x103/μL or ≥3.0 GI/L)
11b. chemistry

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
estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease 
[MDRD]) ≥60 mL/min/1.73 m2 36

total bilirubin level (TBL) ≤1 times ULN

alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1 times 
ULN

alkaline phosphatase (ALP) ≤1 times ULN
Note: Patients with an established diagnosis of Gilbert’s syndrome (requires source 
documentation showing unconjugated hyperbilirubinemia, with no evidence of 
hemolysis) can be included with bilirubin levels ≤3 times ULN.
5.2. Exclusion Criteria
Patients will be excluded from study enrollment if they meet any of the following criteria within 
the screening period, which is 35 days or less prior to the start of study treatment, unless 
specifically defined otherwise.
Gastrointestinal
12.
Have a current diagnosis of Crohn’s disease, inflammatory bowel disease unclassified 
(IBD-U) (formerly known as indeterminate colitis), or UC proctitis (disease limited to 
the rectum, that is, distal to the recto-sigmoid junction, which lies approximately 15 cm 
from anal margin).
13.
Have an inherited immunodeficiency syndrome or a known monogenic cause of 
UC-like colonic inflammation.
14.
Have had or will need abdominal surgery, specifically:
14a. Have had bowel resection or intestinal or intra-abdominal surgery:

Extensive colonic surgery for UC (for example, subtotal colectomy)

Have had any small bowel or colonic surgery within 6 months prior to baseline 
(Visit 2).

Have had any nonintestinal intra-abdominal surgery within 3 months of baseline.
14b. Are likely to require surgery for the treatment of UC during the study.
Note: Patients who have had limited surgery for UC (for example, segmental colonic 
resection) may be allowed in the study, if this does not affect the assessment of 
efficacy. Discussion with the sponsor should occur prior to screening of such patients.
15.
Have evidence of toxic megacolon, intra-abdominal abscess, or stricture/stenosis within 
the small bowel or colon.
Adenoma, Dysplasia, Gastrointestinal Cancer
16.
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17.
Have any current sporadic adenoma without dysplasia (adenomatous polyps occurring 
proximal to known areas of colitis) that has not been removed.
Note: Once the sporadic adenoma without dysplasia is completely removed, the patient 
may be eligible for the study, provided all other study eligibility criteria are met.
18.
Have dysplasia occurring in flat mucosa, sporadic adenomas containing dysplasia, and 
dysplasia-associated lesions or masses (DALMs) as follows:
18a. Any history or current evidence of high-grade dysplasia is exclusionary.
18b. Any history or current evidence of dysplasia occurring in flat mucosa is exclusionary. 
This includes histopathology reporting “indefinite for dysplasia,” low-grade dysplasia, 
and high-grade dysplasia.
18c. Any history or current evidence of a nonadenoma-like DALM, with or without 
evidence of dysplasia, is exclusionary.
18d. Any current sporadic adenoma containing dysplasia or any current adenoma-like 
DALM that has not been removed is exclusionary.
Note: Once the sporadic adenoma containing dysplasia or adenoma-like DALM is 
completely removed, the patient may be eligible for the study, provided all other study 
eligibility criteria are met.
Prior or Current Medications
19.
Have received any of the following for treatment of UC within the time frames listed 
here:
19a. Rectally administered topical corticosteroid therapies (for example, enemas, 
suppositories, foam applications), or a course of IV corticosteroids within 2 weeks prior 
to screening endoscopy.
Note: Patients requiring systemic corticosteroids for non-UC conditions (except 
corticosteroids to treat adrenal insufficiency) are excluded. 
19b. 5-ASA enemas or 5-ASA suppositories within 2 weeks prior to screening endoscopy.
19c. Immunomodulatory medications, including oral cyclosporine, IV cyclosporine, 
tacrolimus, mycophenolate mofetil, thalidomide or JAK inhibitors (for example, 
tofacitinib) within 2 weeks prior to the screening endoscopy.
Note: AZA, 6-MP, and methotrexate are allowed (see Inclusion Criterion 10c). Other 
immunomodulatory medications should be discussed with the sponsor prior to 
screening.
19d. Anti-TNF antibodies (for example, infliximab, adalimumab, or golimumab) within 
4 weeks prior to screening endoscopy.
19e. Anti-integrin antibodies (for example, vedolizumab) within 12 weeks prior to screening 
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Note: This exclusion does not apply if the participant has a result from a validated 
drug-level test demonstrating no drug concentration in the period between last dose and 
the screening visit.
19f. Anti-IL12p40 antibodies (for example, ustekinumab [Stelara®]) or anti-IL-23p19 
antibodies (for example, mirikizumab [LY3074828], risankizumab [BI-655066], 
brazikumab [MEDI-2070], guselkumab [CNTO1959], or tildrakizumab [MK-3222]) 
within 4 weeks prior to screening endoscopy.
19g. Agents that deplete B or T cells (for example, rituximab, alemtuzumab, or visilizumab) 
within 12 months of baseline. Patients remain excluded if there is evidence of persistent 
targeted lymphocyte depletion at the time of screening endoscopy.
19h. Any investigational nonbiologic therapy within 4 weeks prior to the screening 
endoscopy or within 5 half-lives prior to the screening endoscopy, whichever is longer.
19i. Any investigational biologic therapy, not otherwise mentioned, within 8 weeks prior to 
the screening endoscopy or within 5 half-lives prior to the screening endoscopy, 
whichever is longer.
19j. Leukocyte apheresis (leukapheresis, for example, Adacolumn®) within 3 weeks prior to 
screening endoscopy.
19k. Interferon therapy within 8 weeks prior to screening endoscopy.
20.
Have failed 3 or more classes of advanced therapies approved for treatment of UC.
Infections and Infectious Disease
21.
Have or have had active tuberculosis (TB) or latent tuberculosis infection (LTBI):
21a. Have current active TB or past history of active TB (see Section 8.2.6).
21b. Have LTBI, or have had LTBI that has not been treated with a complete course of 
appropriate therapy as defined by the WHO and/or the United States Centers for 
Disease Control and Prevention (see Section 8.2.6).
Note: Patients who have a documented history of completing an appropriate TB 
prophylaxis regimen with no history of risk of re-exposure since completing their 
treatments and with no evidence of active TB may be eligible to participate in the 
study, provided all other study eligibility criteria are met.
22.
Have HIV infection, or AIDS, or test positive for HIV antibodies at screening.
23.
Have a current infection with hepatitis B virus (that is, positive for hepatitis B surface 
antigen [HBsAg] and/or PCR positive for HBV DNA) (Section 8.2.7).
24.
Have a current infection with hepatitis C virus (that is, positive for HCV RNA) 
(Section 8.2.8).
25.
Have C. difficile or other intestinal infection within 30 days of screening endoscopy, or 
test positive at screening for C. difficile toxin or for other intestinal pathogens.
26.
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Note: Patients may be eligible if they have had adequate treatment of this condition and 
have resolution of symptoms at least 3 months prior to screening endoscopy, provided 
all other study eligibility criteria are met.
27.
Have serious, opportunistic, or chronic or recurring extraintestinal infections that are 
not adequately treated or that require antibiotics during the period from 30 days prior to 
screening until baseline (Visit 2). Such infections include, but are not limited to, the 
following:
27a. Serious (requiring hospitalization, and/or IV or equivalent oral antibiotic treatment).
27b. Opportunistic (as defined in Winthrop et al.16)
Note: Active and ongoing Herpes zoster within 8 weeks prior to screening is 
exclusionary. Herpes zoster is considered active and ongoing until all vesicles are dry 
and crusted over.
27c. Chronic or recurrent infections (duration of symptoms, signs, and/or treatment of 
6 weeks or longer)
27d. Recurring (including, but not limited to, herpes simplex, herpes zoster, recurring 
cellulitis, chronic osteomyelitis).
Note: Patients with only recurrent, mild and uncomplicated orolabial, and/or genital 
herpes may be considered for enrollment if discussed with the sponsor’s designated 
medical monitor and if other study eligibility criteria are met. Patients with other 
opportunistic infection or chronic, recurrent extraintestinal infections within 60 days 
before baseline should be discussed on a case-by-case basis with the sponsor's 
designated medical monitor.
28.
Have a nonserious extraintestinal infection that is not adequately treated prior to 
screening and randomization. A patient who develops an extraintestinal infection 
during the screening period must be adequately treated before receiving study drug.
Other Medical Conditions
29.
Have had extra-abdominal surgery and have not recovered fully following surgery, 
including complete wound healing, before screening.
30.
Have a solid organ transplant or hematopoietic stem cell transplantation.
31.
Have a diagnosis or history of malignant disease within 5 years prior to baseline
Exceptions:

Participants with cervical carcinoma in situ that has been resected with no evidence 
of recurrence or metastatic disease for at least 3 years prior to baseline may 
participate in the study, if all other study eligibility criteria are met.

Participants with basal cell or squamous epithelial carcinomas of the skin that have 
been resected with no evidence of metastatic disease for at least 3 years may 
participate in the study, if all other study eligibility criteria are met.


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Protocol J1P-MC-KFAH(b)
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32.
Have an unstable or uncontrolled illness, including but not limited to 
cerebrocardiovascular, respiratory, gastrointestinal (excluding UC), hepatic, renal, 
endocrine, hematologic, neurological disorder, or significant uncontrolled 
neuropsychiatric disorder that would potentially affect a patient's safety within the 
study or else confound efficacy assessments.
33.
Have experienced any of the following within 12 months before screening: myocardial 
infarction, unstable ischemic heart disease, stroke, or New York Heart Association 
Stage IV heart failure.
34.
Have any of the following:

are, in the judgment of the investigator, actively suicidal and therefore deemed to be 
at significant risk for suicide

have answered “yes” to either Question 4 or Question 5 on the “Suicidal Ideation” 
portion of the C-SSRS or have answered “yes” to any of the suicide-related 
behaviors on the “suicidal behavior” portion of the C-SSRS, and the ideation or 
behavior occurred within the past month.
35.
Have experienced a thrombotic event within 24 weeks before baseline, or are on 
anticoagulants, and in the opinion of the investigator are not well-controlled regarding 
management of hypercoagulable risk.
36.
Have a known allergy or hypersensitivity to LY3471851 or any of its excipients, or 
clinically significant multiple or severe drug allergies, or history of severe 
post-treatment hypersensitivity reactions, including, but not limited to, erythema 
multiforme major, linear IgA dermatosis, toxic epidermal necrolysis, or exfoliative 
dermatitis.
37.
Have abnormal laboratory values or ECG abnormalities at screening that, in the opinion 
of the investigator, indicate unacceptable risk for the participant’s safety in the study.
38.
Have a history of chronic alcohol abuse, IV drug abuse, or other illicit drug abuse 
within 1 year before screening.
Note: Marijuana is considered an illicit drug for the purposes of this study, regardless 
of local laws. Cannabidiol products may be used during the study, if they are derived 
exclusively from hemp. Participants who use hemp-based cannabidiol (CBD) products 
must be on a stable dose for at least 10 days prior to randomization, and participants 
must remain on that stable dose during the study.
39.
Have received a Bacillus Calmette-Guerin (BCG) vaccination or treatment within 12 
months before baseline, or have received a live attenuated vaccine within 3 months 
before baseline, or intend to receive such during the study or within 20 weeks after the 
last dose of study drug.
Previous or Concurrent Clinical Trial Participation
40.
Are currently enrolled in any other clinical study involving an IP or any other type of 
medical research judged not to be scientifically or medically compatible with this study.


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Protocol J1P-MC-KFAH(b)
66
41.
Have previously been randomized in this study or have received LY3471851 in any 
previous study.
Note: This criterion does not apply to potential participants who are undergoing 
rescreening procedures.
Other Exclusions
42.
Are unsuitable for inclusion in the study in the opinion of the investigator or sponsor 
for any reason that may compromise the participant’s safety or confound data 
interpretation.
43.
Are unwilling or unable to comply with the use of a data collection device to directly 
record data from the patient daily for the duration of the study, or are unable or 
unwilling to make themselves available for the required number of study visits, or are 
unwilling to complete study procedures and follow the restrictions of the study.
44.
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 drug.
45.
Are investigative site personnel directly affiliated with this study and/or their 
immediate families. Immediate family is defined as a spouse, parent, child, or sibling, 
whether biological or legally adopted.
46.
Are employees of Eli Lilly and Company (Lilly) or are employees of a third-party 
organization involved in the study which requires exclusion of their employees.
5.3. Lifestyle Considerations
Study participants should be instructed not to donate blood or blood products during the study 
and for 20 weeks following their last dose.
To participate in the study, patients must agree to the contraception, reproduction, and 
breastfeeding criteria detailed in Section 5.1, Section 5.2, and Appendix 4.
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study intervention. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to meet the 
CONSORT publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any 
SAE.
5.4.1. Allowed Retesting of Screening Investigations
Retesting of screening investigations (without a requirement for screen failure and rescreening) 
is allowed at the discretion of the sponsor's designated medical monitor. The screening 
investigations specified here may be retested 1 time at the discretion of the investigator:


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
Screening hematology and chemistry blood tests: where results are outside the 
acceptable range for inclusion in the study but may be within the acceptable range for 
inclusion on retesting, due to test-retest variability

Stool testing: if there is a technical difficulty in performing or reporting the C. difficile or 
stool culture assays

Retesting or confirmatory testing with an IGRA: for example, QuantiFERON®-TB 
Gold or T-SPOT® assay (see Section 8.2.6 for details)

Endoscopy: where the endoscopist is unable to adequately visualize the mucosa (for 
example, due to poor bowel preparation or technical issues with equipment) or where the 
central reader is unable to determine the centrally read Mayo ES (for example, failure of 
the recording equipment).
Retesting of all other screening investigations should be discussed with the medical monitor 
prior to retesting.
5.4.2. Rescreening of Individuals Who Fail Screening
Informed consent for rescreenings
Each time an allowed rescreening is performed, the individual must sign a new ICF and will be 
assigned a new identification number (Section 10.1.3).
Procedures not required to be repeated during rescreening
Individuals in rescreening who have already completed the protocol-required screening CXR or 
TB tests are not required to repeat these procedures if they were performed within 90 days before 
the date of signing the rescreening ICF. However, these procedures can be repeated at the 
discretion of the investigator.
Rescreening after failure to meet study entry criteria
The following table describes conditions under which a potential study participant may be 
rescreened. If a participant’s reason for screen failure is not listed in the table, the participant
may not be rescreened.
The interval between the allowed rescreenings should be at least 4 weeks, unless a shorter 
interval has been agreed with the study’s designated medical monitor. The investigator should 
confirm that the patient has a negative C. difficile stool toxin/stool culture/stool ova parasite (as 
applicable) before performing additional rescreening investigations. 


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If a participant is not 
eligible because of this 
entry criterion...
then the participant...
Frequency of allowed 
rescreening for the 
specified criterion
4, 5, 6, 7, 8, 9, 10, 11, 
14, 19, 27, 28, 29, 31, 
32, 38, 39, 40, 42, or 44
may be rescreened when the reason for the screen failure 
has resolved.
up to 2 times, for a 
maximum total of 
3 screenings
17
may be rescreened when the polyps have been removed.
up to 2 times, for a 
maximum total of 
3 screenings
18d
may be rescreened when all of the following have been 
removed: sporadic adenomas containing dysplasia, or 
adenoma like-DALMs containing an area diagnosed as 
“indefinite for dysplasia” or low grade dysplasia.
up to 2 times, for a 
maximum total of 
3 screenings
21b
if completely treated for LTBI.
up to 2 times, for a 
maximum total of 
3 screenings
26
may be rescreened when the reason for the screen failure 
has resolved.
1 time


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6. St u d y I nter ve nti o n
St u d y  int er ve nt i on is defi ne d as a n y i n vesti gati onal i nter ve nt i on, m ar kete d pr o d uct, place b o, or 
me dical de vice i nte n de d t o be a d mi nistere d t o or use d b y a st u d y partici pa nt acc or din g t o t he 
st u d y pr ot oc ol.
6. 1. St u d y I nter ve nti o ns A d mi nistere d
St u d y  int er ve nt i ons
I n Sta ge 1, this st u d y i n v ol ves 2 d ose l e vels o f L Y 3 4 7 1 8 5 1 , as well as place b o. De pe n di n g o n t he 
i nteri m a nal yses a n d sea mless a da pt at i on descri be d i n Sect i on 4. 1 , t he st u d y ma y i n v o l ve t hese 
a n d/ or ot her d ose le vels of  L Y 3 4 7 1 8 5 1, as well as place b o , i n Sta ge 2.
Tre at me nt N a me :
L Y 3 4 7 1 8 5 1
Place b o
D os a ge F or m ul ati o n :
0. 6 -m L vial deli vers
0. 9 m g L Y 3 4 7 1 8 5 1
0. 9 % s o di u m c hl ori de
D os a ge Le vels :
 µ g
 µ g
ne w d ose sa
n ot a p plica ble
R o utes of A d mi nistr ati o n :
s u bc uta ne o us i njecti o n
s u bc uta ne o us i njecti o n
D osi n g I nstr ucti o ns :
d osi n g Q 2 W
d osi n g Q 2 W
a N e w d oses a d de d i n Sta ge 2 ma y be l o wer t ha n  
 µ g or greater b ut will n ot e xcee d  
 µ g .
L Y 3 4 7 1 8 5 1 dr u g pr o d uct will be pr o vi de d as a sterile s ol ut i on i n a si n gle-use vial f or S C 
i njecti on. T he dr u g pr o d uct vials will be s u p plie d i n cart o ns wit h t he a p pr o priate q ua ntit y 
s pecific t o t he pla n ne d dis pe nsi n g sc he d ule. A n u n bli n de d p har macist or ot her u n bli n de d 
q ualifie d i n di vi d ual will pre pare t he st u d y int er ve ntio n f or S C d osi n g (see Secti o n 6. 3 ). W he n 
pre pare d f or d osi n g acc or di n g t o t he detaile d i nstr ucti o ns pr o vi d e d b y t he s p o ns or , it will not be 
p ossi ble t o dist i n g uis h L Y 3 4 7 1 8 5 1 fr o m place b o.
M o ni t ori n g after d ose a d mi nistrati o n
All partici pa nts s h o ul d be m o nit ore d f or 3 0 mi n utes or l o n ger after d osi n g, acc or di n g t o 
i n vesti gat or practice or l ocal sta n dar d of care.
Pac ka gi n g a n d la beli n g
L Y 3 4 7 1 8 5 1 will be s u p plie d b y t he s p o ns or or its desi g nee i n acc or da nce wit h c urre nt G o o d 
Ma n ufact uri n g Practice . Cli nical trial mat erials will b e la bele d acc or di n g t o t he c o u ntr y’s 
re g ulat or y r e q uire me nts. All I Ps will be st ore d, i n ve nt orie d, rec o ncile d, a n d destr o ye d acc or di n g 
t o a p plicable re g ulat i ons.
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6.2. Preparation/Handling/Storage/Accountability
The Pharmacy Preparation Instructions and Pharmacy Manual provide instructions for the 
preparation, handling, and storage of LY3471851 drug product and placebo, and describes site 
responsibility and accountability for the administered products.
Investigators and authorized site personnel should consult the information provided in the 
Pharmacy Preparation Instructions, Pharmacy Manual, or the label for specific preparation and 
administration information, including warnings, precautions, contraindications, adverse 
reactions, and dose modifications.
Preparation
The IPs will be prepared by an unblinded pharmacist (or other unblinded qualified individual) 
who is not involved in any other study-related procedures.
Handling and storage
Follow the storage and handling instructions for the IP, as noted in the IP packaging.
Site responsibilities and accountability
The following are responsibilities of the investigator or his or her designee:

The investigator or designee must confirm appropriate storage conditions have been 
maintained during transit for all study intervention received and that any discrepancies 
are reported and resolved before use of the study intervention.

Only participants enrolled in the study may receive study intervention. 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 site staff.

The investigator or authorized study personnel is responsible for study intervention 
accountability, reconciliation, and record maintenance (that is, receipt, reconciliation, and 
final disposition records).
Further guidance and information for the final disposition of unused study interventions are 
provided in the Pharmacy Manual.
The investigator or designee is also responsible for

explaining the correct use of the study interventions

verifying that instructions are followed properly

maintaining accurate records of IP dispensing and collection, and

returning all unused medication to Lilly or its designee at the end of the study.
Note: In some cases, sites may destroy the material if, during the investigative site selection, the 
evaluator has verified and documented that the site has appropriate facilities and written 
procedures to dispose of clinical materials.


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6.3. Measures to Minimize Bias: Randomization and Blinding
Blinding will be maintained throughout the conduct of the study, as described in the separate 
Unblinding Plan.
Method of treatment assignment
Assignment to treatment groups will be determined by a computer-generated random sequence 
using the IWRS.
The randomization ratios for Stage 1 and Stage 2 are described in Section 9.2.
The randomization will be stratified based on the following factors:

previous advanced therapy failure status (yes/no)

baseline corticosteroid use (yes/no), and

baseline disease activity (MMS: [4 to 6] or [7 to 9]).
Unblinded pharmacist or other qualified individual
Investigators and all individuals involved in administering the blinded treatment or performing 
assessments will remain blinded to each participant’s assigned study intervention throughout the 
course of the study. To maintain this blind, an otherwise uninvolved party (unblinded pharmacist 
or other unblinded qualified individual) will be responsible for the preparation and dispensation 
of all study intervention. Blinded site personnel or blinded designee will administer the study 
intervention to the participant.
Independent evaluation for potential injection site reactions (ISRs)
If a participant spontaneously reports symptoms of an injection site reaction, an authorized
member of the site staff who, in the opinion of the investigator, is qualified to assess reports of 
potential ISRs and who is not involved with any other study procedure will evaluate the 
participant’s report. If signs or symptoms of an injection site reaction are indeed present and 
further evaluation is warranted, this authorized evaluator will contact the investigator’s designee 
or the investigator for further evaluation of the participant’s report. See additional instructions 
provided in Section 8.3.6.3.
Emergency unblinding
Emergency unblinding for AEs may be performed through the IWRS. This option may be used 
ONLY if the participant’s well-being requires knowledge of the participant’s treatment 
assignment. All actions resulting in an unblinding event are recorded and reported by the IWRS.
If, because of emergency unblinding, a participant’s study treatment assignment is unblinded to 
the participant or to blinded site personnel who are performing study assessments, including the 
investigator, the participant must be discontinued from study drug (Section 7.1.1). In cases where 
there are ethical reasons to have the participant remain in the study, the investigator must obtain 
specific approval from the sponsor’s clinical research physician for the participant to continue in 
the study.
In case of an emergency, the investigator has the sole responsibility for determining if unblinding 
of a participants’ intervention assignment is warranted. Participant safety must always be the first 
consideration in making such a determination. If the investigator decides that unblinding is 


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warranted, it is the responsibility of the investigator to promptly document the decision and 
rationale and notify the sponsor as soon as possible.
6.4. Study Intervention Compliance
The date and time of each dose administered will be recorded in the source documents and 
recorded in the eCRF. The dose of study intervention and study participant identification will be 
confirmed prior to the time of dosing. Deviations from the prescribed dosage regimen are 
identifiable via the eCRF.
6.5. Concomitant Therapy
Participants should be instructed to consult authorized site personnel before taking any new 
medications or supplements during the study. Authorized site personnel should consult the 
sponsor’s medical monitor if there are any questions about concomitant therapies during the 
study.
Recording of concomitant therapy
Any medication or vaccine (including over-the-counter, bowel preparations or prescription 
medicines, vitamins, and/or herbal supplements) that the participant is receiving at the time of 
enrollment or receives during the study must be recorded in the Concomitant Medication eCRF 
along with

reason for use

route of administration, and

dates of administration, including start and end dates.
Dosage information including dose level and frequency may also be collected when applicable.
Allowed concomitant therapy
Participants are encouraged to maintain their usual medication regimens for concurrent 
conditions or diseases throughout the study treatment periods, unless those medications are 
specifically excluded (see Appendix 7). Participants taking permitted UC concomitant 
medications are to keep doses stable unless modifications are needed due to AEs, and are to 
follow the instructions regarding dose stabilization in Appendix 8.
Administration of prohibited UC medications, approved or investigational, constitutes treatment 
failure. Use of such medications should not be withheld if, in the opinion of the investigator, 
failure to prescribe them would compromise participant safety. Participants who require a 
prohibited medication to treat their UC must be discontinued from study drug (Section 7.1.1).
If a concomitant medication is needed to treat an AE or for appropriate medical management, the 
investigator should base decisions on the participant and clinical factors, considering prohibited 
medications. A participant who initiates a prohibited medication for a non-UC indication may 
either discontinue the study drug or discontinue the prohibited medication.
Vaccinations
See Appendix 7 and Appendix 8 for requirements on the timing of vaccinations.


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Use of pr o hi bite d me dicati o ns after disc o nt i n uati on of st u d y  dr u g
At  discreti on of t he i n vest i gat or, me dicat i ons liste d i n A p pe n di x 7 are all o we d after a patie nt 
di sc o nti n ues st u d y dr u g a n d c o mpletes t he E T V .
Res c ue t hera p y
T his st u d y  d oes n ot i ncl u de resc ue t hera p y. P artici pa nts w h o are n o nres p o n ders at Wee k 1 2 will 
be assi g ne d t o t he hi g h est d ose of L Y 3 4 7 1 8 5 1 (
 µ g), as descri be d i n Secti o n 4. 1 . If t hese 
parti ci pa nts re mai n n o n res p o n ders at Wee k 2 6, t he y will be disc o nt i n ue d fr om st u d y dr u g a n d 
e nter p ost -treat me nt fol l ow- u p p eri o d ( Secti o n 7. 1. 1 ).
C orti c oster oid t a peri n g
P arti cipa nts w h o e nter t he stu d y o n oral c ortic oster oi d t hera p y  for treat m e nt of t heir U C s h o uld 
mai ntai n t he sta ble d ose of c ortic oster oi d d uri n g t he e nt ire 1 2- wee k i n d ucti o n peri o d. 
P arti cipa nts w h o ac hie ve cli nical res p o nse at Wee k 1 2 will i nit iate c ortic oster oi d ta peri n g, as 
des cri be d bel o w. F or partici pa nts w h o ca n n ot t olerate t he c ortic oster oi d ta per wit h o ut rec urre nce 
of  cli nical s y m pt o ms, c ortic oster oi d ta per ma y be pa use d a n d/ or c ortic oster oi d d ose ma y be 
i ncrease d u p t o t he ori gi nal d ose at i n d ucti on baseli ne (s h o ul d n ot e x cee d i n d uct i on baseli ne 
d ose). I n s uc h cases, atte m pts t o rei nit iate c ortic oster oi d ta peri n g s h o ul d be ma de withi n 2 wee ks 
of  int err u pti o n of ta per, wit h a g oal t o c o m plete ta peri n g n o later t ha n Wee k 2 6.
Wee k 1 2 cli nical n o nres p o n ders w h o u n der g o e xte n de d
i n d ucti on wi t h t he hi g h d ose of 
L Y 3 4 7 1 8 5 1 will be gi n c ortic oster oi d ta peri n g if cli nical res p o nse is ac hie ve d at Wee k 2 6. F or 
parti ci pa nts w h o ca n n ot t olerate t he c ortic oster oi d ta per wit h o ut rec urre nce of cli nical s y m pt o ms, 
c ortic oster oid ta per m a y b e p ause d a n d/ or c ortic oster oi d d ose ma y be i ncrease d u p t o t he ori gi nal 
d ose at i n d uct i on baseli ne (s h o ul d n ot e xcee d i n d ucti o n baseli ne d ose). I n s uc h cases, atte m pts t o 
rei nitiate c ortic oster oi d ta peri n g s h o ul d be ma de withi n 2 wee ks of i nterr u pti o n of ta per , wit h a 
g oal  t o c o mplete ta peri n g n o later t ha n Wee k 4 0.
T he rec o m me n de d ta peri n g sc he d ule f or oral c ortic oster oi ds ( ot her t ha n b u des o ni de e xte n de d 
r elease ta blets [ b u des o nide M M X] or becl o m et has o ne dipr o pi o nate [ gastr o -resista nt pr ol o n ge d 
r elease ta blet] ) is as fol l ows.
D ose > 1 0 m g/ da y  pre d nis o ne or e q ui vale nt: ta per dail y d ose b y 5 mg/ wee k u nt il 
recei vi n g 1 0 m g/ da y, a n d t he n c o nti n ue ta peri n g at 2. 5 m g/ wee k u nt il 0 m g/ da y .
D ose ≤1 0 m g/ da y pre d nis o ne or e q ui vale nt: ta per dail y  d ose b y 2. 5 mg/ wee k u nt il 
0 m g/ da y.
T he rec o m me n de d ta peri n g sc he d ule f or partici pa nts recei vi n g oral b u des o ni de M M X 9 m g/ da y 
is t o re d uce ta blets t o 9 m g e ver y ot her da y for 2 wee ks, f o ll owe d b y 9 m g e ver y  t hir d da y f or 
2 wee ks, a n d t he n disc o nt i n ue.
T he rec o m me n de d ta peri n g sc he d ul e for parti ci pa nts recei vi n g oral becl omet has o ne di pr o pi o nate 
( gastr o-resista nt pr olo n ge d -release ta blet) 5 mg/ da y  is t o re d uce ta blets t o 5 m g e ver y ot her da y 
f or 4 wee ks, a n d t he n disc o nti n ue.
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6. 6. D ose M o dific ati o n
T h e a da pti ve desi g n of t his st u d y all ows t he i ntr o d uctio n of  ne w d ose le vels of  L Y 3 4 7 1 8 5 1 after 
t he i nteri m a nal yses f or Sta ge 1, as descri be d i n Secti o n 4. 1 a n d Secti o n 6. 1 . I n all sta ges a n d 
st u d y p erio ds, t he ma xi m u m d ose will n ot e xcee d  
 µ g.
N o ot her d ose m o dificati o ns are per mitte d, e xce pt f or reas o ns of i m me diate partici pa nt safet y.
6. 7. I nter ve nti o n after t he E n d of t he St u d y
L Y 3 4 7 1 8 5 1 will n ot be a vaila ble t o partici pa nts f oll o wi n g c o m plet i on of t he st u d y .
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7. Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal
These sections describe reasons for a participant’s

permanent or temporary discontinuation of study drug (Section 7.1), or

discontinuation (withdrawal) from the study (Section 7.2).
Discontinuation of specific sites or the trial as a whole (“stopping rules”) are handled as part of 
regulatory, ethical, and trial oversight considerations in Section 10.1.9.
7.1. Discontinuation of Study Intervention
Study drug may be permanently discontinued or temporarily withheld during the study.
Participants who permanently discontinue study drug early will undergo early termination 
procedures, which include

an ETV, and

post-treatment follow-up visits, as shown in the SoA.
7.1.1. Criteria for Permanent Discontinuation of Study Drug
Data collection and safety follow-up when study drug is permanently discontinued
In rare instances, it may be necessary for a participant to permanently discontinue (definitively 
discontinue) study intervention.
If study intervention is permanently discontinued, the participant will remain in the study to be 
evaluated at the ETV and post-treatment follow-up visits.
See the SoA for data to be collected at the time of discontinuation and follow-up and for any 
further evaluations that need to be completed. Safety follow-up is as outlined in the SoA, Section 
8.2, and Section 8.3.
Criteria for permanent discontinuation of study drug
Possible reasons for permanent discontinuation of study drug include, but are not limited to, the 
following:
Participant decision

The participant requests to discontinue the study drug.
Pregnancy

The participant becomes pregnant during the study (see Section 8.2.5.1). Pregnant 
patients will not undergo an endoscopy at the ETV.
Safety considerations

The participant develops any of the following conditions during the study:


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o
malignancy (except for successfully treated basal or squamous cell skin 
carcinoma)
o
dysplasia occurring in flat mucosa
o
dysplasia-associated lesion or mass (DALM)
o
HIV infection/acquired immune deficiency syndrome (AIDS)
o
active TB infection or untreated LTBI (Section 7.1.2; Section 8.2.6)
o
HCV RNA positive (Section 8.2.8)
o
HBV DNA positive and clinical assessment consistent with HBV reactivation

Note: The HBV DNA result is to be confirmed if initial positive test 
result is positive but below the level of quantification (Section 7.1.2; 
Section 8.2.7). The participant is to be referred to, evaluated, and 
managed by a specialist physician with expertise in evaluation and 
management of viral hepatitis prior to discontinuation of any 
immunomodulatory and/or immunosuppressive therapy, including study 
drug. Timing of discontinuation from study drug relative to the initiation 
of any antiviral treatment for hepatitis is to be based on the 
recommendation of the consulting specialist physician, in conjunction 
with the investigator, and aligned with medical guidelines and standard of 
care.

The participant requires a colectomy, proctocolectomy, or partial colectomy during the 
study.

The investigator, after consultation with the sponsor’s designated medical monitor, 
determines that a systemic hypersensitivity reaction has occurred and is related to study 
drug administration.

The participant has any of the following results on 2 consecutive samples taken at least 
48 hours, but no more than 1 week, apart:
o
Total WBC <1000 cells/μL
o
ANC <500 cells/μL
o
ALC <200 cells/μL
o
Hemoglobin <6.5 g/dL

The participant develops CRS. In consultation with the Lilly medical monitor, if an AE is 
deemed possibly or probably due to CRS based on the details and severity of clinical 
signs and symptoms, time course of symptom onset relative to study drug administration, 
and if possible, a cytokine panel from a blood sample obtained at the time of the event, 


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Protocol J1P-MC-KFAH(b)
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the participant will be discontinued from study treatment, and will continue safety 
follow-up.

The participant develops hypereosinophilia.
o
Participants with absolute eosinophil counts >1500 cells/µL and signs and/or 
symptoms of target organ involvement that is not consistent with UC and/or with 
the participant’s UC and medical history will be discontinued from study drug in 
consultation with the medical monitor. Participants will undergo appropriate 
medical evaluation, which should take into account the participant’s known UC 
and past medical history according to the participant’s history and medical 
records, including previous imaging, biopsies and laboratory findings. Evaluation 
of target organ involvement will involve additional diagnostic tests as 
appropriate, including laboratory tests, imaging (for example, echocardiogram, 
chest x-ray, CT scan), and biopsies. New onset cardiac, pulmonary, and skin 
findings in the setting of peripheral eosinophilia will be considered as target 
organ involvement, unless attributable to other causes.
o
Asymptomatic participants with an absolute eosinophil count >5000 cells/µL 
should have a repeat measurement to confirm the count. If the count is confirmed, 
the participant will be permanently discontinued from study drug and undergo 
appropriate medical evaluation.

The participant has an AE, SAE, or a clinically significant change in a laboratory value 
that, in the opinion of the investigator, merits the discontinuation of the study drug and 
appropriate measures being taken.
Hepatic event or liver test abnormality

Participants who are discontinued from study drug because of a hepatic event or liver test 
abnormality should have additional hepatic safety data collected via the hepatic eCRF 
packet. Discontinuation of study drug because of abnormal liver tests should be 
considered by the investigator when a participant meets 1 of the following conditions 
after consultation with the sponsor’s designated medical monitor (see Section 8.2.9):
o
ALT or AST >8 times ULN
o
ALT or AST >5 times ULN sustained for more than 2 weeks
o
ALT or AST >3 times ULN and TBL >2 times ULN or INR >1.5
o
ALT or AST >3 times ULN with the appearance of fatigue, nausea, vomiting, 
right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)
o
ALP >3 times ULN
o
ALP >2.5 times ULN and TBL >2 times ULN, or


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Protocol J1P-MC-KFAH(b)
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o
ALP >2.5 times ULN with the appearance of fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%).
Other reasons for permanent discontinuation of study drug

The participant
o
scores a 3 for Item 12 (Thoughts of Death or Suicide) on the QIDS-SR16 at any 
time in the study, or
o
reports suicidal ideation or suicidal behaviors during the study.
Note: A psychiatrist or appropriately trained professional may assist in the 
decision to discontinue the participant from study drug.

The participant requires treatment for exacerbation of UC and the treatment involves 1 or 
more medications at doses higher than those specified in the “dose stabilization” 
inclusion criterion; for example, the participant requires prednisone >20 mg/day) (see 
Appendix 8).

The participant requires treatment with prohibited medications specified in the 
“prohibited medications” exclusion criterion, for example, a course of IV corticosteroids 
or a single dose of infliximab or IV cyclosporine (see Appendix 7).

The participant was nonresponder at Week 12 and remains a treatment nonresponder at 
Week 26.

Unblinding: If an investigator, blinded site personnel or blinded designees who are 
performing assessments, or the participant is unblinded to a participant’s treatment 
assignment because of an emergency unblinding as described in Section 6.3, the 
participant must be discontinued from the study drug and continue to post-treatment 
follow-up. In cases where there are ethical reasons to have the participant continue on 
study drug, the investigator must obtain specific approval from the sponsor’s designated 
medical monitor for the participant to continue.
Note: The presence or absence of an ISR will not be considered an unblinding event; 
participants with an ISR may remain in the study and continue to receive study drug, and 
this will not be considered a protocol deviation.
7.1.2. Criteria for Temporary Interruption (Withholding) of Study Drug
7.1.2.1. Infection-Related Criteria for Temporary Interruption of Study Drug
Temporary withholding of study drug is required for the development of any of the following 
infection-related criteria during the study:


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Protocol J1P-MC-KFAH(b)
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
Serious or opportunistic infections, as defined in Section 5.2. Study drug is to be withheld 
until resolution of all acute clinical signs and symptoms, and completion of all 
appropriate anti-infective treatment (exception for LTBI).

Participants diagnosed with LTBI during the study are to be permanently discontinued 
from study drug unless the participant is a candidate for LTBI treatment, and is treated 
for LTBI as follows:
o
Study drug is temporarily withheld for at least the first 4 weeks of LTBI 
treatment.
o
After receiving at least 4 weeks of appropriate LTBI therapy (as per WHO and/or 
the United States Centers for Disease Control guidelines), if there is no evidence 
of hepatotoxicity (ALT/AST must remain ≤2 times ULN) or other treatment 
intolerance, study drug may be resumed.
o
The participant must complete appropriate LTBI therapy to remain eligible to 
receive study drug.

HBV DNA results that are reported as positive, or as detecting HBV DNA, but HBV 
DNA is below the level of quantification. The sponsor’s designated medical monitor 
should be contacted regarding study status of the participant. HBV DNA testing is to be 
repeated as soon as is feasible. If HBV DNA is confirmed as positive, the participant 
must be permanently discontinued from study drug (Section 7.1).
7.1.2.2. Other Criteria for Temporary Interruption of Study Drug
This table lists criteria for interrupting study drug administration and conditions.
Interrupt study drug if the participant...
Resume study drug administration after...
requires major surgery.
adequate wound healing has occurred.
has AEs or abnormal laboratory values which, 
in the opinion of the investigator, have an 
unclear relationship to study drug.
consultation with the sponsor's designated medical monitor, 
when investigator and the medical monitor agree that 
resumption of study drug is appropriate for the participant.
Except in an emergency, the investigator should consult with sponsor’s designated medical 
monitor whenever possible before temporarily interrupted study drug, or for resuming 
temporarily interrupted study drug, for any reasons not specified in this protocol.
7.2. Participant Discontinuation/Withdrawal from the Study
Participant discontinuation (withdrawal from the study) is expected to be uncommon.
A participant may withdraw from the study in the following circumstances:

at any time at his or her own request, or at the request of his or her designee (for example, 
parents or legal guardian)

at the discretion of the investigator for safety, behavioral, compliance, or administrative 
reasons


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Protocol J1P-MC-KFAH(b)
80

if the participant enrolls in any other clinical study involving an IP or enrolls in any other 
type of medical research judged not to be scientifically or medically compatible with this 
study, or

if the participant, for any reason, requires treatment with another therapeutic agent that 
has been demonstrated to be effective for treatment of the study indication. In this case, 
discontinuation from the study occurs prior to introduction of the new agent.
Data collection and follow-up for participants who discontinue the study
At the time of discontinuing from the study, an ETV should be conducted, if possible, as shown 
in the SoA. See the SoA for data to be collected at the time of study discontinuation and follow-
up and for any further evaluations that need to be completed. The participant will be permanently 
discontinued both from the study drug and from the study at that time.
No follow-up procedures will be performed for a participant who withdraws informed consent,
unless he or she has explicitly provided permission and consent.
Withdrawal of consent for disclosure
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a participant 
withdraws from the study, he or she may request destruction of any samples taken and not tested, 
and the investigator must document this in the site study records.
7.2.1. Discontinuation of Inadvertently Enrolled Participants
If the sponsor or investigator identify a participant who did not meet enrollment criteria and was 
inadvertently enrolled, then the participant should be discontinued from study treatment, unless 
there are extenuating circumstances that make it medically necessary for the participant to 
continue on study treatment. If the investigator and the sponsor's clinical research physician 
agree it is medically appropriate to continue, the investigator must obtain documented approval 
from the sponsor clinical research physician to allow the inadvertently enrolled participant to 
continue in the study with or without treatment with IP. Safety follow up is as outlined in the 
SoA, Section 8.2, and Section 8.3.
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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Protocol J1P-MC-KFAH(b)
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8. Study Assessments and Procedures
Study procedures and their timing are summarized in the SoA. Adherence to the study design 
requirements, including those specified in the SoA, is essential and required for study conduct.
All blinded assessments and sample collections should be completed before a dose is 
administered at the dosing visits.
8.1. Efficacy Assessments
This study uses components and permutations of the Mayo score17 to assess UC disease activity 
for the primary and several secondary endpoints, as defined in the table below. 
Complete and accurate daily recording of the Mayo SF and RB subscores by participants in their 
daily eDiary is necessary for the success of the study. Adequate bowel preparation and an 
endoscopy with adequate visualization of the mucosa will enable calculation of the Mayo ES.
Endpoint
Definition
Clinical remission
SF subscore = 0, or SF = 1 with a decrease of ≥1 point from baseline, and
RB subscore = 0, and
ES = 0 or 1, excluding friability
Clinical response
A decrease in the MMS of ≥2 points and ≥30% decrease from baseline, and
A decrease of ≥1 point in the RB subscore from baseline or a RB score of 0 or 1
Endoscopic remission
Mayo ES = 0 or 1, excluding friability
Endoscopic response
A decrease in the Mayo ES of ≥1 point compared to baseline
Symptomatic remission
SF = 0, or SF = 1 with a decrease of ≥1 point from baseline, and
RB = 0
Symptomatic response
≥30% decrease from baseline in the composite clinical endpoint of the sum of SF 
and RB subscores
Histologic remission
Geboes score <2 or Geboes subscores = 0 for Grade 2a, 2b, 3, 4, and 5 (equivalent 
definitions)
Histologic-endoscopic 
mucosal healing
Geboes score <2 AND endoscopic remission
Abbreviations: ES = endoscopic subscore; MMS = modified Mayo score; RB = rectal bleeding; SF = stool 
frequency.


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82
8.1.1. Primary Efficacy Assessment
8.1.1.1. Primary Endpoint
The primary endpoint is clinical remission at Week 12. Clinical remission is based on the MMS 
and is defined in Section 8.1.
8.1.1.2. Mayo Score
The Mayo score is a composite instrument comprised of the following subscores:
Stool Frequency: The SF subscore is a participant-reported measure. This item reports the 
number of stools in a 24-hour period, relative to the normal number of stools for that 
participant in the same period, on a 4-point scale. A stool is defined as a trip to the toilet 
when the participant has either a bowel movement, or passes blood alone, blood and mucus, 
or mucus only. The total number of stools passed in a 24-hour period will be recorded by the 
participant in a daily eDiary. The reference “normal” SF for that participant will be recorded 
electronically at the screening visit. Study software will use the participant-reported daily SF 
and the reference normal SF to automatically calculate the Mayo SF subscore. The 
participant will record this in an electronic diary. Further details on the analysis of daily diary 
items are contained in the SAP.
The Normal SF is a participant-reported measure. This item reports the number of stools in a 
24-hour period when the participant was in remission or, if the participant has never achieved 
remission, the reported SF before initial onset of signs and symptoms of UC. Remission 
refers to a period of time since being diagnosed with UC when the participant is not 
experiencing any signs or symptoms relating to UC. This period of time may last a few 
weeks or a few months, or may even last several years. The participant will record this 
electronically as source data at the screening study visit.
Note: The “Remission/Normal Stool Frequency (SF)” question should be explained to 
the participant before the participant answers the question to ensure accurate participant 
understanding and data capture. Errors made by the participant cannot be corrected once 
the response is saved and confirmed.
Rectal Bleeding: The RB subscore is a participant-reported measure. This item reports the 
most severe amount of blood passed per rectum for a given day, on a 4-point scale. The 
participant will record this in a daily electronic diary.
Endoscopic Subscore: The ES is a physician-reported measure that reports the worst 
appearance of the mucosa on flexible sigmoidoscopy or colonoscopy, on a 4-point scale. 
Determination of the ES is further detailed in Section 8.1.1.3. Consistent with current clinical 
practice and regulatory advice, this study excludes friability from the definition of an ES 
of 1.
Physician’s Global Assessment: The PGA is a physician-reported measure that summarizes 
the investigator’s assessment of the participant’s UC disease activity on a 4-point scale.
Assessment of the PGA score will be collected by the investigator or designee at appropriate 
study visits and entered into the eCRF. Consistent with regulatory guidance, the PGA will 
not be used as an efficacy assessment in this study.


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
8 3
Eac h s u bsc ore is sc ore d o n a 4 -p oi nt scale, ra n gi n g fr o m 0 t o 3, t o gi ve a ma xi m u m Ma y o sc ore 
of  1 2. T he M M S is a s u m of t he Ma yo S F, R B , a n d E S, gi vi n g a ma xi m u m M M S of 9. 
A d dit i onal sc ori n gs i n v ol vi n g t he Ma yo sc ore (f or e xa m ple,
ha ve bee n descri be d a n d 
ma y be use d i n a nal yzi n g data fr o m t his st u d y.
See A p pe n di x 9 f or more i nf or m at i on a b o ut t he Ma y o sc ore .
See A p pe n d i x 1 1 f or more i nf or m at i on a b o ut t he dail y electr o nic diar y.
8. 1. 1. 3. E n d osc o p y
E n d osc o p y  will be use d t o deter mi ne t he Ma y o E S at scree ni n g a n d at ot her visits, as n ote d o n 
t he S o A. T he Ma y o E S will be deter mi ne d b y

bli n de d rea di n gs p erf or me d b y  site pers o n nel or t heir desi g nees, a n d

bli n de d ce ntral rea ders .
N ote: Disa gree me nt bet wee n t he site rea der a n d ce ntral rea der will be a dj u dicate d b y a n 
a d ditio nal  bli n de d ce ntral rea der, as detaile d i n t he I ma ge Re vie w c harter.
A fle xi ble si g m oi d osc o p y or c olo n osc o p y  will be perf or me d o n all partici pa nts d uri n g scree ni n g, 
wi t hi n 1 4 da ys pri or t o ra n d o mizati on. T he e n d osc o p y  re p ort a n d hist o pat h ol o g y re p ort (if 
bi o psies are se nt t o t he l ocal hist o pat h ol o g y la b orat or y) must be a vaila ble i n t he s o urce 
d oc u m e nts. Prior t o perf or mi n g t he scree ni n g e n d osc o p y, i n vesti gat ors or desi g nees s h o uld 
e ns ure t hat partici pa nts ha ve cli nicall y acce pta ble ce ntral la b orat or y  test res ults, i ncl u di n g st o ol 
tests t hat are “ ne gati ve” f or C. difficile a n d ot her i ntesti nal pat h o ge ns (see Secti o n 5 ).
Fle xi ble si g m o i d osc o p y is rec o m me n de d f or all partici pa nts, e xce pt t he f oll owi n g parti ci pa nts 
f or w h om c olo n os c o p y  is t he re q uire d e n d osc o pic pr oce d ure at scree ni n g:
1.
P arti cipa nts w h o re q ui re s ur veilla nce f or U C-ass ociate d d ys plasia a n d mali g na nc y, w h o 
ha ve n ot ha d a s ur veilla nce c o l on osc o p y , i ncl u di n g ra n d o m a n d tar gete d bi o psies, wit hi n 
1 2 m o nt hs of baseli ne. T hese i ncl u de
p artici pa nts wit h pa nc olitis of greater t ha n 8 years’ d urati o n
p artici pa nts wit h left-si de d c olitis of greater t ha n 1 2 years’ d urati o n , or
p artici pa nts wit h pri mar y scler osi n g c h ola n gitis.
I n t hese partici pa nts, t he i n vesti gat or or desi g nee ca n o btai n a d dit i onal bi o psies t o 
s ur veille f or d ys plasia at t he scree ni n g c ol o n osc o p y. T his scree ni n g c olo n osc o p y  will be 
perf or me d acc or di n g t o l o c al  g uideli nes , a n d bi o psies will be se nt t o t he l ocal 
hist o pat h ol o g y  la b orat or y. C hr o moe n d osc o p y  ma y be a n acce pta ble met h o d of tar geti n g 
bi o psies, if all o we d acc or di n g t o l o c al  g uideli nes.
2.
P arti cipa nts w h o re q ui re scree ni n g f or c ol orectal ca ncer, w h o d o n ot ha ve a c urre nt 
scree ni n g c ol o n osc o p y acc or di n g t o l ocal g ui deli nes. T hese ma y i ncl u de

p artici pa nts wit h fa mil y hist or y of c olorectal  ca ncer
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84

personal history indicating increased colorectal cancer risk, for example, previous 
adenomatous polyps, or

participants 50 years or older, or with other known risk factor.
3. Participants who do not have the report of a completed, full colonoscopy available in 
source documents to establish extent of the disease. Participants with rectal sparing on 
baseline endoscopy must have documentation of rectal involvement on a prior 
endoscopy.
4. Participants for whom, in the opinion of the investigator, a colonoscopy is indicated at 
screening, for example, to confirm that a recent removal of an adenomatous polyp is 
complete prior to randomization.
If a participant already has up-to-date surveillance for dysplasia and/or up-to-date screening for 
colorectal cancer, the endoscopy report and histopathology report (if applicable) used to support 
this must be available in the source documents, in order to satisfy study entry criteria (Section 5).
Participants who undergo colonoscopy at screening do not require a separate flexible 
sigmoidoscopy in the same screening period.
At Week 12 (or ETV), a flexible sigmoidoscopy is recommended for all participants. 
Colonoscopy can be performed instead of flexible sigmoidoscopy at Week 12 for clinically 
indicated reasons in the judgement of the investigator and after discussion with the 
sponsor-designated medical monitor, as appropriate. The endoscopy report and histopathology 
report (if biopsies are sent to the local histopathology laboratory) must be available in the source 
documents. Participants who undergo a flexible sigmoidoscopy at an ETV will not undergo 
additional endoscopies within the study. Participants who discontinue the study drug because of 
pregnancy will not undergo a flexible sigmoidoscopy at their ETV.
If a participant undergoes early termination soon after screening endoscopy, the need for ETV 
endoscopy should be discussed with the sponsor's designated medical monitor. There is no need 
for an ETV endoscopy if fewer than 16 weeks have elapsed since a prior endoscopy.
The endoscopist will be a licensed physician, who is qualified by education, training, and
experience to perform colonoscopies. Investigators may delegate endoscopy to other authorized 
site personnel. However, authorized site personnel performing endoscopy must receive training 
from the sponsor or designee in the determination and calculation of the Mayo ES. The 
endoscopist will determine the site-read Mayo ES at each endoscopy, and site personnel or their 
designee will record this in the eCRF.
All endoscopic procedures will be video recorded using a storage medium provided by the 
sponsor or designee. The video images will be sent for independent central reading. A detailed 
Image Review charter from the central reading laboratory will outline the standard study 
procedures used to capture and transmit video recordings of endoscopic procedures throughout 
the study, and will outline the qualifications required of the central reader. Recorded endoscopy 
procedures (without participant identifying information) will be used for research purposes.
The central reader will determine the centrally-read Mayo ES at each colonoscopy in a blinded 
manner, as detailed in the Image Review charter.


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
8 5
T he a dj u dicate d Ma y o E S will be pr o vi de d t o t he site pri or t o ra n d o mizati o n t o e na ble 
deter mi nat i on of t he M M S f or eli gi bilit y. A n e n d osc o pi c Ma yo sc ore , as deter mi ne d b y t he 
I ma ge Re vie w c harter , will be use d f or e n d p oi nt deter mi nati on a n d cli nical res p o n der stat us.
8. 1. 2. Sec o n d ar y Effic ac y Assess me nts
S ec o n dar y efficac y e n d p o i nts are base d o n 

sc ores deri ve d fr o m t he Ma yo sc ore t o ol descri be d i n Secti on 8. 1. 1. 2 ,

sc ores fr om t he Ge b oes sc ore f or t he assess me nt of h ist olo gical  a cti vit y, or 

pati e nt -re p orte d o utc o me i nstr u me nts.
8. 1. 2. 1. E n d osc o pic Bi o psies
A hist o pat h ol o g y  re p ort s u p p orti n g t he dia g n osis of U C m ust be a vaila ble i n t he s o urce 
d oc u m e nts prior t o ra n d o mizat i on, i n or der t o satisf y  st u d y e ntr y crit eria ( Sectio n 5 ). If a 
hist o pat h ol o g y  re p ort is n ot a vaila ble, t he in vest i gat or or desi g nee ca n o btai n a d dit i onal bi o psies 
f or t his p ur p ose at t he scree ni n g e n d osc o p y (se nt t o t he lo c al  hist o pat h olo g y  la b orat or y).
Bi o psies will be o btai ne d at eac h e n d osc o p y  t o s u p p ort assess me nt of t he hist o pat h ol o g y 
e n d p o i nts i n t his st u dy a n d, w here per mitte d, f or f urt her researc h p ur p oses ( wit h o ut partici pa nt 
i de ntif yi n g i nf or mati on), i ncl u di n g t he assess me nt of
T hese will be se nt 
t o t he ce ntral st u d y la b orat or y for pr ocessi n g. Hi st o pat h olo gi c sc ori n g of t hese bi o psies will be 
perf or m e d b y a bli n de d ce ntral rea der. A detaile d hist o pat h ol o g y  c harter will o utli ne t he 
pr oce d ures t o be use d f or sec ure s peci me n tra nsfer, pr ocessi n g, sli de pre parati o n , a n d digi tizat i on 
of  sli des f or hist o pat h ol o gic sc ori n g. T hese res ults will n ot be ma de a vaila ble t o st u d y  sites.
8. 1. 2. 2. Ge b oes Sc ore
T he Ge b oes scale is base d o n a c o mpre he nsi ve gra di n g s yste m t hat e val uates as pects of m uc osal 
i nj ur y see n i n U C , i ncl u di n g cr y pt arc hitect ure, la mi na pr o pria c hr o nic i nfla m mati on, l a mi na 
pr o pria e osi n o p hils, la mi na pr o pria ne utr o p hils, i ntrae pit helial ne utr o p hils, cr y pt destr ucti o n, a n d 
s urface e pithelial i nj ur y. F or eac h of t he hist ol o gical feat ures assesse d, t he hi g hest gra de i n 
w hic h t here is e vi de nce of disease is assi g ne d. T he Ge b oes sca le is f urt her descri be d i n A p pe n di x 
1 0 .
8. 1. 2. 3 . P atie nt -Re p orte d O utc o me I nstr u me nts
T he f oll owi n g are pati e nt -re p orte d o utc o me i nstr u me nts c ollecte d usi n g a partici pa nt e Diar y:

Rectal  Blee di n g

St o ol  Fre q ue nc y

N oct ur nal  St o ol 

Bri st ol St o ol Scale

Ur ge nc y N R S
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
8 6

A b d o mi nal Pai n N R S

Fat i g ue N R S, a n d

P G R - S
T he f o ll owi n g are pati e nt -re p orte d o utc o me i nstr u me nts c ollecte d electr o nicall y:

P G I- C a n d

I B D Q
A p pe n di x 1 1 c o ntai ns descri pti o ns of t hese pat ient -re p orte d o utc o me i nstr u me nts.
8. 1. 3. E x pl or at or y Effic ac y Assess me nts
8. 2. S afet y Assess me nts
Vi sits a n d or der of safety assess me nts
S af et y assess me nts occ ur as s pecifie d i n t he S o A.
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
8 7
If m ult i ple safety assess me nts are sc he d ule d f or t he sa me visit, t he preferre d or der of c o m plet i on 
is
1.
E C G a n d t he n vital si g ns
2.
ot her safet y assess me nts, i ncl u di n g p h ysical e xa mi nat i ons a n d n o nlea di n g (s p o nta ne o us) 
A E c ollect i on, f o ll owe d b y C -S S R S ( Secti o n 8. 2. 1 0 ), a n d fi nall y
3.
bl o o d sa m ple c ollect i on f or cli nical la b orat or y, P K, P D, p har mac o ge net ic, bi omar ker, a n d 
testi n g.
Data c ollect i on a n d re p orti n g
T he A E data c ollect i on a n d re p orti n g re q uire me nts are descri be d i n Secti o n 8. 3 a n d A p pe n di x 3 . 
A d dit i onal re q uire me nt s re gar di n g ( A E SIs are descri be d i n Secti on 8. 3. 6 .
A n y cli nicall y  sig nifica nt fi n di n gs t hat res ult i n a dia g n osis a n d t hat occ ur after t he partici pa nt 
recei ves t he first d ose of st u d y dr u g s h o uld be re p orte d t o Lill y  or its desi g nee as a n A E via 
e C R F.
S af et y m o nit ori n g
T he pri nci ple i n vest i gat or will m onit or t he safet y data t hr o u g h o ut t he st u d y . I m me diate safety 
c o ncer ns s h o ul d be disc usse d wit h t he s p o ns or i m me diatel y u p o n occ urre nce or a ware ness t o 
deter mi ne w het her t he part ici pa nt s h o ul d c o nti n ue or disc o nti n ue t he st u d y i nter ve nt i on.
T he s p o ns or will m o nit or t he safet y data, i ncl u di n g A Es, S A Es , disc o nti n uati ons, vital si g ns, a n d 
cli nical la b orat or y res ults b y mea ns of bli n de d re vie ws perf or me d at least q uarterl y a n d b y ot h er 
a p pr o priate met h o ds. T hese met h o ds i ncl u de re vie ws b y a f u nct i onall y  in de pe n de nt safet y  
p h ysicia n a n d/ or cli nical researc h scie ntist w h o re g ularl y  re vie ws S A E re p orts i n real ti me a n d 
acr oss st u dies, a n d w h o re vie ws a p plica ble cli nical safet y a n d e pid e m i ol ogical p u blicat i ons fr om 
t he literat ure. If t his safet y m o nit ori n g u nc o vers a n iss ue t hat nee ds t o be a d dresse d b y 
u n bli n di n g at t he i n di vi d ual or gr o u p le vel, a d dit i onal a nal yses of t he safet y data ca n be 
perf or m e d b y t he s p o ns or’s i n de pe n de nt i nter nal s afet y re vie w c om mittee.
A p pr o priate ness of safet y assess me nts
T he safet y assess me nts use d i n t his st u d y are r o uti ne ele me nts of cli nical healt h assess me nt a n d 
P hase 2 dr u g de vel o p me nt.
8. 2. 1. Vit al Si g ns
Vi t al si g ns ( bl o o d press ure, b o d y te m perat ure, a n d p ul se rate) will be meas ure d w he n s pecifie d 
i n t he S o A a n d as cli nicall y i n dicate d. A d dit i onal vit al si g ns ma y be meas ure d d uri n g st u d y visits 
if warra nte d, as deter mi ne d b y t he i n vesti gat or.
Bl o o d press ure a n d p ulse rate s h o ul d be meas ure d after t he partici pa nt has bee n sitt i n g f or at 
least 5 mi n utes.
U nsc he d ule d ort h ostatic vital si g ns s h o ul d be assesse d, if p ossi ble, d uri n g a n y A E of  dizzi ness or 
p ost ure -i n d uce d s y m pt o ms. If t he partici pa nt feels u na ble t o sta n d, sitti n g or s u pi ne vital si g ns 
will b e rec or de d.
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C O N FI D E N TI A L
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8 8
8. 2. 2. P h ysic al E x a mi n ati o ns
P h ysical e xa mi nat i ons will be perf or me d w he n s pecifie d i n t he S o A . P h ysical e xa mi nati ons m a y 
als o be perf or me d as cli nicall y in dicate d at ot her visit s, at t he discreti on of t he i n vesti gat or.
P h ysical e xa mi nat i on at scree ni n g
At  scree ni n g, t he c o m plete p h ysical e xa mi nati on s h o ul d i ncl u de t he f o ll owi n g re gi o ns a n d b o d y  
s yste ms:

ge neral a p peara nce

s ki n

hea d, ears, e y es, n ose, t hr oat

l y m p h n o des

car dio vasc ular

res pir at or y

a b d o mi nal

e xtre mit ies, a n d

ne ur o l ogi c.
Pel vic, rectal, a n d breast e xa ms are n ot re q uire d u nless cli nicall y i n dicate d.
T he scree ni n g p h ysical e xa mi nati o n s h o ul d i ncl u de a n assess me nt of T B ris k fact ors a n d 
s y m pt o ms or si g ns of T B, i ncl u di n g a n assess me nt of peri p heral l y m p h n o des.
H ei g ht ( wi t ho ut s h oes ) a n d wei g ht will als o be meas ure d a n d rec or de d.
S y m pt o m -di recte d ph ysical e xa mi nat i ons after scree ni n g
After scree ni n g, p h ysical e xa mi nat i ons s h o ul d i ncl u de a s y m pt o m -di recte d e val uati on, as well as 
e xa mi nat i on of e yes, heart, l u n gs, a b d o me n, a n d vis ual e xa mi nat i on of t he s ki n ( ot her t ha n area 
c o vere d b y clot hi n g or ot her m at erial). At a p pr o xi matel y e ver y t hir d t o fo urt h m o nt h after 
scree ni n g, t he p h ysical e xa mi nati on s h o ul d als o i ncl u de a n assess me nt of T B ris k fact ors a n d 
s y m pt o ms or si g ns of T B, i ncl u din g a n assess me nt of peri p heral l y m p h n o des ( Secti o n 8. 2. 6 ).
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8.2.3. Electrocardiograms
For each participant, 12-lead ECGs will be collected when specified in the SoA. The ECGs 
should be recorded before collecting any blood for safety or PK tests. Participants must be supine 
for approximately 5 to 10 minutes before ECG collection and remain supine, but awake, during 
ECG collection.
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.
ECGs will be interpreted by a qualified physician (the investigator or qualified designee) as soon 
after the time of ECG collection as possible, and ideally while the participant is still present, to 
determine whether the participant meets the study entry criteria and for immediate participant 
management, should any clinically relevant findings be identified.
If a clinically significant finding is identified (including, but not limited to changes from baseline 
in QT/QTc interval) after enrollment, the investigator or qualified designee, in conjunction with 
the sponsor’s medical monitor, will determine whether the participant can continue in the study 
and if any change in participant management is needed.
The review of the ECG printed at the time of collection must be documented. Any new clinically 
relevant finding should be reported as an AE.
8.2.4. Chest Radiography
A posterior–anterior CXR, interpreted and reported by a radiologist or pulmonologist, will be 
obtained when specified in the SoA.
A lateral CXR can also be obtained if, in the opinion of the investigator, a lateral view is 
indicated.
Note: Participants do not need to have a CXR at screening if, based on the judgment of the 
investigator, both of the following 2 conditions are met:

the CXR was performed within 3 months before initial screening, and

documentation of the CXR, read by a qualified radiologist or pulmonologist, is sufficient 
for TB evaluation according to local standard of care.
For each participant, the CXR films, images, or a radiology report must be available to the 
investigator for review before the participant is randomized. Certain findings from the CXR may 
be consistent with a condition that excludes a participant from the study (see Section 5.2).
Note: Results of a chest CT scan or other imaging study similar to a CXR may be substituted in 
place of the CXR as described above, in consultation with the sponsor’s medical monitor.
8.2.5. Laboratory Tests
Appendix 2 lists the clinical laboratory tests to be performed, and the SoA specifies when 
samples are routinely collected for clinical laboratory tests. Samples for laboratory testing will be 
obtained in the event of anaphylaxis or generalized urticaria, as described in Section 8.3.6.1 and


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Appendix 2, Section 10.2.2. Additional tests may be performed at any time during the study, as 
determined necessary by the investigator or as required by local regulations.
All protocol-required laboratory assessments, as defined in Appendix 2, must be conducted in 
accordance with the SoA, standard collection requirements, and laboratory manual.
If laboratory values from nonprotocol 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, AE, or dose 
modification), then report the information as an AE.
Reviewing and recording test results
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.
Repeat testing after clinically significant abnormal findings
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 8 weeks after the last dose of study intervention should be repeated until 
the values return to normal or baseline or are no longer considered clinically significant by the 
investigator or the medical monitor. If such values do not return to normal/baseline within a 
period of time judged reasonable by the investigator, the etiology should be identified and the 
sponsor notified.
Blinding of laboratory test results
Laboratory results that could unblind the study will not be reported to investigative sites or other 
blinded personnel.
Sample retention
Unless otherwise specified in the subsections of Section 8 or in Appendix 1, Section 10.1.12, all 
samples collected for specified laboratory tests will be destroyed within 60 days of receipt of 
confirmed test results. Certain samples may be retained for a longer period, if necessary, to 
comply with applicable laws, regulations, or laboratory certification standards.
8.2.5.1. Pregnancy Testing
Pregnancy testing is to be performed on WOCBP and women with a history of tubal ligation. 
Participants who are pregnant will be discontinued from the study (Section 7).
Pregnancy testing visits and times
Serum pregnancy test will be done at screening only, and results will be confirmed by the central 
laboratory.
Urine pregnancy testing will be performed locally when specified in the SoA. If the specified 
visit includes study drug administration, the urine pregnancy test must be “negative” within 
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Urine pregnancy testing may be performed at additional time points during the study treatment 
period and/or follow-up period, at the discretion of the investigator or if this is required by local 
regulations.
If a urine pregnancy test is not available, a local serum pregnancy test is an acceptable 
alternative.
Optional FSH testing
The participant’s FSH level can be obtained during screening at the discretion of the investigator 
to assist in determining whether a woman meets the definition of “postmenopausal.” The FSH 
level can also be optionally obtained during the study to determine the participant’s 
postmenopausal status (see the SoA and Appendix 4).
8.2.6.Tuberculosis Testing and Monitoring
Tuberculosis testing
During screening, all participants are to be assessed for risk factors, symptoms, and signs of TB 
with all of the following:

Thorough history to determine the lifetime risk factors for 
o
TB infection
o
TB progression, and
o
symptoms and/or signs of active TB, and

Signs of previous or active TB by means of
o
thorough physical examination for signs of active TB, including

measurement of body temperature (Section 8.2.1), and

assessment of peripheral lymph nodes (Section 8.2.2), and
o
posterior-anterior CXR interpreted and reported by radiologist or pulmonologist 
(Section 8.2.4).
All participants with no history of LTBI or active TB, and no history of positive Mantoux TST 
using PPD or positive Mycobacterium tuberculosis IGRA must have 1 of the following:

PPD TST
o
The TST is performed by injecting 0.1 mL of tuberculin PPD into the inner 
surface of the forearm. The injection should be made with a tuberculin syringe, 
with the needle bevel facing upward. The TST is an intradermal injection. When 
placed correctly, the injection should produce a pale elevation of the skin (a 
wheal) 6 to 10 mm in diameter. Measure induration at site of intradermal 


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injection 48 to 72 hours after intradermal injection. The test must be read during 
this window of time. The reaction should be measured in millimeters of 
induration (palpable, raised, hardened area, or swelling). The reader should not 
measure erythema (redness). The diameter of the indurated area should be 
measured across the forearm (perpendicular to the long axis).
o
An induration of 5 or more millimeters is considered positive.
o
Two-step testing (repeat TST from 1 to 3 weeks after the first TST) is 
recommended for certain participant groups, based on investigator judgment, 
including

persons receiving immunosuppressant treatment

persons with a history of temporally remote increased risk of TB 
infection, and

persons for whom the first test is negative, as per local public health 
and/or professional medical society recommendations.

IGRA for Mycobacterium tuberculosis. Ensure that specimen handling, transport, timing, 
and laboratory procedures meet all requirements per package insert.
Retesting
One retest is allowed for participants with an “indeterminate” QuantiFERON-TB Gold assay or 
“borderline” T-SPOT.TB assay. Participants with 2 indeterminate QuantiFERON-TB Gold 
assays or 2 borderline T-SPOT.TB assays will be excluded.
Diagnosed LTBI
Participants diagnosed with LTBI, or have had LTBI that has not been treated with a complete 
course of appropriate therapy as defined by the WHO and/or the United States Centers for 
Disease Control and Prevention, are excluded (Section 5.2).
Monitoring during the study
For all participants, monitoring for TB is to be continuous throughout the study. At a minimum, 
each participant is to have the following documented at least approximately every 3 to 4 months:

thorough history to determine any risk factors for TB infection and for TB progression, 
symptoms or signs of active TB, and

physical examination that includes assessment for signs of active TB, including 
measurement of body temperature and assessment of peripheral lymph nodes 
(Section 8.2.2).
8.2.7. Hepatitis B Testing and Monitoring
Initial testing for HBV infection includes hepatitis B surface antigen (HBsAg) and antibody to 
hepatitis B core antigen (anti-HBc).


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
If HBsAg is positive, the participant is excluded.

If HBsAg is negative and anti-HBc is negative, the participant is not excluded.

If HBsAg is negative and anti-HBc is positive, further testing for HBV DNA is required.
o
If the screening HBV DNA is positive, the participant is excluded.
o
If the screening HBV DNA is negative, the participant is not excluded. Repeat 
testing for HBV DNA is required at least approximately every 8 to 14 weeks 
during the study (see the timing in the SoA), with temporary withholding or 
permanent discontinuation of study intervention if HBV DNA is positive, as 
described in Section 7.
Management of enrolled participants with detectable HBV DNA during the study
If HBV DNA is detected during the study, the study drug will be temporarily withheld or 
discontinued and participants should receive appropriate follow-up medical care as described in 
Section 7.
8.2.8. Hepatitis C Testing and Monitoring
Initial testing for HCV infection includes testing for antibodies to HCV.

If anti-HCV is positive, a serum test for circulating HCV RNA is required.

If HCV RNA test is negative, the participant is not excluded.

If HCV RNA test is positive, the participant is excluded (see Section 5.2).
Participants who have had HCV infection and been successfully treated, defined as a sustained 
virologic response (HCV RNA by PCR negative for at least 24 weeks following treatment 
completion) are not excluded on the basis of HCV, as long as HCV RNA test is negative at 
screening.
If HCV RNA is detected during the study, the study drug will be discontinued (see Section 7), 
and the participant should receive appropriate follow-up medical care.
8.2.9. Hepatic Safety Monitoring
Close hepatic monitoring
The laboratory tests listed in Appendix 5, including ALT, AST, ALP, TBL, direct bilirubin, 
GGT, and CK, should be repeated within 48 to 72 hours to confirm the abnormality and to 
determine whether it is increasing or decreasing, if any of the conditions listed in this table occur.
If a participant has the following elevations:
ALT or AST ≥3 times ULN
ALP ≥2 times ULN
TBL ≥2 times ULN (except for patients with Gilbert’s syndrome)
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
TBL = total bilirubin level; ULN = upper limit of normal.


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If the abnormality persists or worsens, clinical and laboratory monitoring, and evaluation for the 
possible causes of the abnormal liver tests should be initiated by the investigator in consultation 
with the sponsor’s designated medical monitor. At a minimum, this evaluation should include a 
physical examination and a thorough medical history, including symptoms, recent illnesses (for 
example, heart failure, systemic infection, hypotension, or seizures), recent travel, history of 
concomitant medications (including over-the-counter), herbal and dietary supplements, history of 
alcohol drinking, and other substance abuse.
Initially, monitoring of symptoms and hepatic biochemical tests should be done at a frequency of 
1 to 3 times weekly, based on the participant’s clinical condition and hepatic biochemical tests. 
Subsequently, the frequency of monitoring may be lowered to once every 1 to 2 weeks, if the 
participant’s clinical condition and lab results stabilize. Monitoring of ALT, AST, ALP, and 
TBL should continue until levels normalize or return to approximate baseline levels.
Comprehensive hepatic evaluation
A comprehensive evaluation should be performed to search for possible causes of liver injury, if 
1 or more of the conditions listed in this table occur:
If a participant has the following elevations:
ALT or AST ≥3 times ULN with hepatic signs/symptomsa, or
ALT or AST ≥5 times ULN
ALP ≥3 times ULN
TBL ≥2 times ULN (except for patients with Gilbert’s syndrome)
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
TBL = total bilirubin level; ULN = upper limit of normal.
a
Hepatic signs/symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, fever, 
rash, and/or eosinophilia >5%.
At a minimum, this evaluation should include a physical examination and a thorough medical 
history, as outlined above, as well as 

tests for prothrombin time (PT-INR)

tests for viral hepatitis A, B, C, and E, and

tests for autoimmune hepatitis, and an abdominal imaging study (for example, ultrasound 
or CT scan).
Based on the participant’s history and initial results, further testing should be considered in 
consultation with the sponsor’s designated medical monitor, including tests for 

hepatitis D virus (HDV)

cytomegalovirus (CMV)

Epstein-Barr virus (EBV)

acetaminophen levels

acetaminophen protein adducts

urine toxicology screen


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
Wilson’s disease

blood alcohol levels

urinary ethyl glucuronide, and 

serum phosphatidylethanol.
Based on the circumstances and the investigator’s assessment of the participant’s clinical 
condition, the investigator should consider referring the participant for a 

hepatologist/gastroenterologist consultation

magnetic resonance cholangiopancreatography (MRCP)

endoscopic retrograde cholangiopancreatography (ERCP)

cardiac echocardiogram, or 

liver biopsy.
8.2.9.1. Additional Hepatic Data Collection in Participants Who Have Abnormal Liver 
Tests During the Study
Additional hepatic safety data collection (hepatic safety eCRF) should be performed for 
participants who meet 1 or more of the following conditions:

Elevation of serum ALT to ≥5 times ULN on 2 or more consecutive blood tests 

Elevated TBL to ≥2 times ULN (except for cases of known Gilbert’s syndrome)

Elevation of serum ALP to ≥2 times ULN on 2 or more consecutive blood tests 

Hepatic event considered to be an SAE.

Discontinuation of study drug due to a hepatic event (Section 7.1).
Note: The interval between the 2 consecutive blood tests should be at least 2 days.
8.2.10. Suicidal Ideation and Behavior Risk Monitoring
Participants should be monitored appropriately and observed closely for suicidal ideation and 
behavior or any other unusual changes in behavior, especially at the beginning and end of the 
course of intervention. Participants who have signs of suicidal ideation or behavior should be 
considered for discontinuation of study drug, following a risk assessment (see Section 7). See 
Section 8.3.1.1 for timing of AE collection relative to collection of the C-SSRS.
8.2.10.1. Columbia Suicide-Severity Rating Scale
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 (NIMH) trial group (TASA) for the purpose of being 
counterpart to the Columbia Classification Algorithm of Suicide Assessment (C-CASA) 
categorization of suicidal events.


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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.
The C-SSRS data will entered in the eCRF.
8.2.10.2. Depression Assessment with 16-Item Quick Inventory of Depressive 
Symptomatology–Self Report
The QIDS-SR16 is a self-administered, 16-item instrument intended to assess the existence and 
severity of symptoms of depression as listed in the American Psychiatric Association’s 
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition.19 A participant is asked to 
consider each statement as it relates to the way he or she has felt for the past 7 days. There is a 
4-point scale for each item ranging from 0 to 3. The 16 items corresponding to 9 depression 
domains are summed to give a single score ranging from 0 to 27, with higher scores denoting 
greater symptom severity. The domains assessed by the instrument include 
1) sad mood
2) concentration
3) self-criticism
4) suicidal ideation
5) interest
6) energy/fatigue
7) sleep disturbance (initial, middle, and late insomnia or hypersomnia)
8) decrease/increase in appetite/weight, and 
9) psychomotor agitation/retardation.
The QIDS-SR16 data will be collected via a tablet device and/or a web-based collection system.
8.3. Adverse Events and Serious Adverse Events
Adverse 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 the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study intervention or study procedures, or that 
caused the participant to discontinue the study intervention or the study (see Section 7).
Pregnancy after maternal or paternal exposure to IP does not meet the definition of an AE. 
However, to fulfill regulatory requirements, any pregnancy should be reported using the SAE 
process described in Section 10.3.4, to collect data on the outcome for both mother and fetus. See 
also Section 8.3.5.


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8.3.1. Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event 
Information
All AEs will be collected from the time of the participant’s signing of the ICF until the 
participant’s last post-treatment follow-up visit.
Likewise, all SAEs will be collected from the signing of the ICF until the last post-treatment 
follow-up visit.
Adverse events that begin before the start of study intervention but after signing of the ICF will 
be recorded on the Adverse Event eCRF.
Although all AEs after signing the ICF are recorded by the site in the eCRF/electronic data entry 
tool, SAE reporting to the sponsor begins after the participant has signed the ICF and has 
received study drug. However, if an SAE occurs after signing the ICF but prior to receiving 
study drug, the SAE needs to be reported ONLY if the SAE is considered reasonably possibly 
related to study procedures.
All SAEs will be recorded and reported to the sponsor or the sponsor’s designee immediately, 
and under no circumstance should this exceed 24 hours, as indicated in Appendix 3, 
Section 10.3.4. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available.
Investigators are not obligated to actively seek AE or SAEs after the conclusion of study 
participation, that is, once the participants have discontinued and/or completed the study (the 
Participant Study Disposition eCRF has been completed). However, if the investigator learns of 
any SAE, including a death, at any time after a participant has been discharged from the study, 
and the investigator considers the event to be reasonably related to the study intervention or 
study participation, the investigator must promptly notify the sponsor.
8.3.1.1. Adverse Event Monitoring with a Systematic Questionnaire
Nonleading (spontaneous) AE collection should occur before the collection of the C-SSRS.
If a suicide-related event is discovered during the C-SSRS collection, but was not captured 
during the nonleading AE collection, sites should not change the AE form. However, if an AE is 
serious or leads to discontinuation, the AE should be included on the AE form. Also, the process 
for reporting SAEs should be followed.
8.3.2. Method of Detecting Adverse Events and Serious Adverse Events
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 3, Section 10.3.3 and 
Section 10.3.4.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about AE 
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8.3.3. Follow-up of Adverse Events and Serious Adverse Events
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs as well as AESIs, as defined in Section 8.3.6, 
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. Further information on follow-up procedures is 
provided in Appendix 3, Section 10.3.3.
8.3.4. Regulatory Reporting Requirements for Serious Adverse Events
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, IRB/ IEC, and investigators.
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (for example, summary or listing of SAEs) from the sponsor will review and 
then file it along with the IB and will notify the IRB/IEC, if appropriate according to local 
requirements.
8.3.5. Pregnancy
For female participants and female partners of male participants, details will be collected for all 
pregnancies occurring from after the start of study intervention and until 12 weeks after the last 
dose.
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of learning 
of the pregnancy and should follow the reporting procedures outlined in Appendix 4, Section 
10.4.3.
Abnormal pregnancy outcomes (for example, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs.
8.3.6. Adverse Events of Special Interest
Adverse events of special interest for this study include

systemic allergic/hypersensitivity reactions, including CRS

serious infections and opportunistic infections, and

injection site reactions.
If such AESIs are reported, sites will be prompted to collect additional data as described in the 
following subsections.


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8.3.6.1. Systemic Hypersensitivity Reactions
Many drugs, but particularly biologic agents, carry the risk of systemic hypersensitivity 
reactions. If such a reaction occurs, additional data describing each symptom should be provided 
to the sponsor in the eCRF. 
Sites should have appropriately trained medical staff and appropriate medical equipment 
available when the study participants are receiving study drug. It is recommended that 
participants who experience a systemic hypersensitivity reaction be treated per national and 
international guidelines.
Blood sample collection for systemic allergic/hypersensitivity events, including cytokine release 
syndrome
In the case of generalized urticaria or anaphylaxis, additional samples as described in
Appendix 2, Section 10.2.2 should be collected. Laboratory results are provided to the sponsor 
via the central laboratory.
8.3.6.2. Serious Infections and Opportunistic Infections
Completion of the Infection eCRF page is required for each infection reported as an AE or SAE. 
The sponsor will identify infections considered to be opportunistic based on the article by
Winthrop et al.16 (see Appendix 6).
8.3.6.3. Injection Site Assessment
Symptoms of a local injection site reaction may include erythema, induration, pain, pruritus, and 
edema.
If a participant reports symptoms (that is, an unsolicited event, volunteered by participant) and
the investigator’s designee or the investigator determines that a clinically relevant injection site 
reaction has occurred, the event will be captured in the eCRF as an AE. In addition, the injection 
site reaction form in the eCRF will be completed. The event will be followed up to completion.
See Section 6.3 for activities relating to injection site reactions.
8.3.7. Complaint Handling
A product complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, safety, effectiveness or performance of a 
trial intervention. The sponsor collects product complaints on IPs and drug delivery systems used 
in clinical studies in order to ensure the safety of study participants, monitor quality, and to 
facilitate process and product improvements.
Participants will be instructed to contact the investigator as soon as possible if they have a 
complaint or problem with the IP so that the situation can be assessed.
Note: Any AEs/SAEs that are associated with a product complaint will follow the processes 
outlined in Section 8.3.3 and Appendix 3.
Time period for detecting product complaints
Product complaints that result in an AE will be detected, documented, and reported to the 
sponsor during all periods of the study in which the drug/device is used. If the investigator learns 


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of any product complaint at any time after a participant has been discharged from the study, and 
such problem is considered reasonably related to a drug/device provided for the study, the 
investigator will promptly notify the sponsor.
Prompt reporting of product complaints to the sponsor
Product complaints will be reported to the sponsor within 24 hours after the investigator becomes 
aware of the complaint. The Product Complaint Form will be sent to the sponsor by methods
designated by the sponsor.
Follow-up of product complaints
Follow-up applies to all participants, including those who discontinue study intervention. The 
investigator is responsible for ensuring that follow-up includes any supplemental investigations 
as indicated to elucidate the nature and/or causality of the product complaint. New or updated 
information will be recorded on the originally completed form with all changes signed and dated 
by the investigator and submitted to the sponsor.
8.4. Treatment of Overdose
For this study, an overdose of LY3471851 is considered any dose greater than the highest dose 
planned to be used in this study. The treatment for suspected overdose is supportive care.
In the event of an overdose, the investigator should:
1. Contact the sponsor’s medical monitor immediately.
2. Closely monitor the participant for any AE, SAE, or laboratory abnormalities for at least 
12 weeks.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the sponsor’s medical monitor based on clinical evaluation of the participant.
8.5. Pharmacokinetics
Pharmacokinetic sample visits and times
At the visits and times specified in the SoA, venous blood samples will be collected to determine 
the plasma concentrations of LY3471851. The actual date and time (24-hour clock time) of 
dosing and sample collection must be recorded accurately on the appropriate forms.
Collection, handling, and analysis of pharmacokinetic samples
Instructions for the collection and handling of blood samples will be provided by the sponsor. 
Samples will be analyzed at a laboratory approved by the sponsor. Concentrations of LY3471851 
will be assayed using a validated PK assay. Analyses of samples collected from participants 
while receiving placebo are not planned.
Additional and unused pharmacokinetic samples
A maximum of 3 additional samples may be collected at additional time points during the study,
if warranted and agreed upon between both the investigator and sponsor. Any excess samples 
collected for PK testing may be used for exploratory analyses, such as bioanalytical methods 


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development, assay validation or cross-validation exercises, protein binding, and/or metabolism 
work.
In the case of systemic allergic/hypersensitivity reactions, additional blood samples will be 
obtained for PK analyses (Section 8.3.6.1).
Blinding pharmacokinetic data
Drug concentration information that may unblind the study will not be reported to investigative 
sites or to personnel who are blinded to study data.
Pharmacokinetic sample retention
The purpose of retention, the maximum duration of retention, and facility for long-term storage 
of samples is described in Appendix 1, Section 10.1.12.
8.6. Pharmacodynamics
The PD biomarkers to be measured include changes in T-cell subsets.
Pharmacodynamic biomarker sample visits and times
At the visits and times specified in the SoA, blood samples will be collected for the exploratory 
analysis of PD biomarkers.
Pharmacodynamic biomarker sample retention
The purpose of retention, the maximum duration of retention, and facility for long-term storage 
of samples is described in Appendix 1, Section 10.1.12.
8.7. Genetics
Where local regulations and IRB/IEC allow, a whole blood sample will be collected from 
consenting participants, as specified in the SoA, for pharmacogenetic analysis .
Genetic sample use
Samples will not be used to conduct unspecified disease or population genetic research either 
now or in the future. Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and 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. 
Samples may be used for research related to LY3471851 and its mechanism of action, the drug 
target, genetic variants thought to play a role in UC, on the disease process and pathways 
associated with the disease or related diseases. The samples may also be used to develop tests or 
diagnostic tools or assays related to UC or to LY3471851. The samples may also be used to 
investigate variable exposure or response to LY3471851. The assessment of variable response 
may include evaluation of AEs or differences in efficacy.


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Molecular technologies are expected to improve during storage period and therefore cannot be 
specifically named. However, existing genetic research approaches include whole genome or 
exome sequencing, genome-wide association studies, and candidate gene studies. Regardless of 
technology utilized, genotyping data generated will be used only for the specific research scope 
described in this protocol. The samples may be analyzed as part of single or multi-study 
assessment of genetic factors involved in the response to LY3471851 or to study interventions of 
this class to improve understanding of the disease or related conditions, and additional analyses 
may be conducted, if necessary, to further understand the clinical data of this study.
Genetic sample confidentiality
All samples will be coded with the participant number. These samples and any data generated 
can be linked back to the participant only by the investigative site personnel. The sponsor will 
store the blood and/or DNA samples in a secure storage space with adequate measures to protect 
confidentiality.
Genetic sample retention
Samples will be retained at a facility selected by the sponsor or its designee. Samples will be 
retained as long as research on the study indication, study intervention, or the class of study 
intervention continues, but no longer than the maximum retention time specified in Appendix 1, 
Section 10.1.12.
8.8. Biomarkers
The following samples will be collected at the visits and times specified in the SoA, where local 
regulations allow:

serum

plasma

whole blood RNA

whole blood epigenetic samples for nonpharmacogenetic biomarker research

fecal matter, and

colonic tissue samples.
Biomarker sample use
Samples may be used for research on the 

drug target

disease process

variable response to LY3471851

pathways associated with UC

mechanism of action of LY3471851, and/or 


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
1 0 3

researc h met h o ds or i n vali dati n g dia g n ostic t o ols or assa ys relate d t o U C or t o 
L Y 3 4 7 1 8 5 1.
Bi o m ar ker sa m ple c o nfi de nt iality
All sa m ples will be co d e d wi t h t he partici pa nt n u m ber. T hese sa m ples a n d a n y data ge nerate d 
ca n be li n ke d bac k t o t he partici pa nt o nl y b y t he i n vesti gati ve site pers o n nel.
Bi o m ar ker sa m ple rete nti o n
T he p ur p ose of rete nti o n, t he ma xi m u m d urati o n of rete nt i on, a n d facilit y f or l on g -t er m st ora ge 
of  sa m ples is descri be d i n A p pe n di x 1 , Sectio n 1 0. 1. 1 2.
8. 1 0. Me dic al Res o urce Utiliz ati o n a n d He alt h Ec o n o mics
T his sect i on is n ot a p plica ble.
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1 0 4
9. St atistic al C o nsi der ati o ns
9. 1. St atistic al H y p ot heses
T he n ull h y p ot hesis f or t he pri mar y  e n d p oi nt is t hat t here is n o differe nce bet wee n L Y 3 4 7 1 8 5 1 
a n d place b o i n in d uci n g cli nical re missi o n i n patie nts wit h m o deratel y t o se verel y  acti ve U C, as 
meas ure d b y t he pr o p orti o n of st u d y  partici pa nts i n cli nical re missi o n at Wee k 1 2.
9. 2. S a m ple Size Deter mi n ati o n
A p pr o xi matel y  2 0 0 t otal  parti ci pa nts, i n t otal, ma y be ra n d omize d acr oss all st u d y sta ges.

D uri n g Sta ge 1, a p pr o xi matel y 1 0 0 partici pa nts will be ra n d o mize d t o 1 of  3 treat me nt 
gr o u ps i n a 2: 2: 1 rati o:
o
a hi g h d ose (
 µ g) of  L Y 3 4 7 1 8 5 1
o
a l ower (
 µ g) d ose of L Y 3 4 7 1 8 5 1, or
o
pl ace b o.

D uri n g Sta ge 2, u p t o a p pr o xi matel y 1 0 0 a d ditio nal  p arti ci pa nts will be ra n d o mize d . As 
state d i n Secti o n 4. 1 , Sta ge 2 will ha ve a place b o gr o u p a n d ma y ha ve m o re L Y 3 4 7 1 8 5 1
treat me nt gr o u ps t ha n Sta ge 1, or fe wer , base d o n decisi o ns ta ke n after t he l ast i nteri m 
a nal ysis of Sta ge 1 . T he ra n d o mizat i on rati o f or Sta ge 2 will deter mi ne d a n d d oc u me nte d 
as part of t he decisi o n- ma k i n g a b o ut t he n u m ber of treat me nt gr o u ps. T his decisi o n 
ma ki n g will occ ur f o ll owi n g Sta ge 1 , a n d t he c h o ice i n all ocat i on rati o m a y b e a djuste d t o 
ac hie ve t he pla n ne d all o cat i on acr oss treat me nt ar ms.
T he p o wer calc ulat i ons f or t his st u d y ass u me t he f oll o wi n g:

At  e n d of st u d y, t hree n o n-pl ace b o treat me nt gr o u ps will ha ve sa m ple size of 
a p pr o xi matel y eit her 4 0, 6 0, or 8 0 patie nts.

At e n d of st u d y, t he place b o gr o u p will ha ve a sa m ple size of a p pr o xi matel y 4 0.

F or t he sa ke of si m plicit y i n t he p o wer calc ulati on,  it is ass u me d t hat t here is n o 
differe nce i n treat me nt effect bet wee n a d va nce d t hera p y-faile d a n d c o n ve nti onal -faile d 
pati e nts. T o si m plif y, it is als o ass u me d t hat all tr e at me nt gr o u ps ha ve t he sa me treat me nt 
effect.

It is ass u me d t hat t he tr ue place b o res p o nse rate is a p pr o xi matel y 5 % a n d t he tr ue 
treat me nt res p o nse is a p pr o xi matel y 3 5 %.

P o wer is calc ulate d f or 3 tests, 1 f or eac h treat me nt gr o u p a gai nst place b o, a n d a dj ust f or 
m ult i ple c o m paris o ns usi n g t he c o nser vat i ve B o nferr o ni a dj ustme nt . P o wer is calc ulate d 
usi n g a fa mil y-wise err or rate of α =. 0 5.
Gi ve n t he se ass u m pt i ons, t he p o wer t o reject t he n ull h y p ot hese s for t he treat me nt gr o u p s wit h 
sa m ple sizes e q ual t o 4 0 , 6 0, a n d 8 0 are 8 9. 5 % , 9 4. 5 %, a n d 9 6. 5 % , res pecti vel y. As a n e xa m ple, 
in a fi xe d desi g n, wi t h t he pl ace b o a n d L Y 3 4 7 1 8 5 1 treat me nt gr o u ps eac h ha vi n g 8 0 parti ci pa nts, 
a 1 7 % or lar ger differe nce bet wee n t he gr o u ps ca n be detecte d wit h 9 0 % p o wer a n d ass u mi n g a 
5 % pl ace b o effect .
C CI
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9.3. Populations for Analyses
This table describes the populations planned for use in the analyses. The mITT population, as 
defined below, will be used in analyses of efficacy and PRO, unless otherwise noted in the SAP.
Population
Description
ITT Population
All randomized participants. Participants will be analyzed according to the 
treatment to which they were assigned.
mITT Population
All randomized participants who receive at least 1 dose of study treatment 
(regardless of whether the participant fails to receive the correct treatment, or 
otherwise fails to follow the protocol). Participants will be analyzed 
according to the treatment to which they were assigned.
Safety Population
Same as mITT population
Pharmacokinetic Evaluable
All participants who receive at least 1 dose of investigational product and 
have sufficient blood sampling to allow for pharmacokinetic evaluation.
Abbreviations: GCP = Good Clinical Practice; ITT = intent-to-treat; mITT = modified intent-to-treat; SAP = 
statistical analysis plan.
9.4. Statistical Analyses
9.4.1. General Considerations
Statistical analysis of this study will be the responsibility of Lilly or its designee.
Efficacy analyses will be conducted on the mITT population. Safety analyses will be conducted 
on the mITT population (Safety Population). The efficacy analysis of the primary endpoint and 
secondary endpoints will be repeated for ITT population. Additional safety analyses may be 
performed as deemed appropriate.
The baseline MMS is calculated from valid daily diary entries obtained prior to endoscopy 
during the screening period and the endoscopic appearance of the mucosa at this screening 
endoscopy. For other efficacy, health outcome and safety assessments, baseline is defined as the 
last non-missing assessment recorded on or prior to the date of the randomization visit (Visit 2).
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. Unless otherwise specified, variables will be analyzed in the original scale on which 
they are measured. The parametric approach will be employed by default for statistical analysis 
except when nonparametric analysis, such as by a rank-based method, is considered to be more 
fitting. Additional exploratory analyses of the data will be conducted as deemed appropriate.
Unless otherwise specified, analysis of hypotheses will be tested without multiplicity control at a 
significance level of 0.05. A 2-sided 95% CI will be provided along with the p-value. For other 
analyses, statistical tests without multiplicity control will be conducted using a 2-sided 
significance level of 0.05. The corresponding p-value along with its 95% 2-sided CI will be 
provided. Additional analyses may also include subgroup analyses for the primary and the 
secondary endpoints.


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For assessments of the primary endpoint and other categorical efficacy endpoints, the CMH 
chi-square test will be used to compare the treatment groups with the following factors:  

previous advanced therapy failure status (yes/no)

baseline corticosteroid use (yes/no)

baseline disease activity (MMS: [4 to 6] or [7 to 9]), and

region (North America/Europe/Other).
The CMH chi-square p-value and the relative risk along with its 2-sided CI will be provided. In 
addition, the absolute treatment difference in proportions will be provided along with the 2-sided 
CI estimate. The differences between each treatment group and placebo will also be tested 
separately using a logistic regression model that controls for at least previous advanced therapy 
failure status (yes/no) and corticosteroid use (yes/no). If deemed necessary, additional analyses 
of categorical efficacy variables may be conducted to address sparse data and/or small sample 
sizes.
Treatment comparisons of continuous efficacy and health outcome variables with multiple 
postbaseline time points will be made using MMRM analysis. The MMRM will include the 
following effects and covariates:

treatment group

previous advanced therapy failure status (yes/no)

corticosteroid use (yes/no)

disease activity (MMS: [4 to 6] or [7 to 9]) at baseline)

region (North America/Europe/Other)

baseline value in the model

visit, and 

the interactions of treatment-by-visit and baseline-by-visit as fixed factors.
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 heterogeneous autoregressive covariance structure, will be 
used. The Kenward-Roger method 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.
Treatment comparisons of continuous efficacy and health outcome variables with a single 
postbaseline time point will be made using ANCOVA with the following in the model:  

treatment group

previous advanced therapy failure status (yes/no)

corticosteroid use (yes/no)

disease activity (MMS: [4 to 6] or [7 to 9]) at baseline)

region (North America/Europe/Other), and


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
baseline value.
Type III sums of squares for LS means will be used for statistical comparison between treatment 
groups. The LS mean difference, standard error, p-value, and 95% CI, unless otherwise 
specified, will also be reported. Missing data imputation method for the ANCOVA model will be 
specified 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 will be conducted as deemed appropriate.
The SAP will be finalized prior to unblinding or interim analysis, whichever occurs first. The 
SAP will include a more technical and detailed description of the statistical analyses described in 
this section. This section is a summary of the planned statistical analyses of the primary and 
secondary endpoints.
9.4.1.1. Estimands
The estimand35 associated with each endpoint and analysis is documented in this table.
Estimand Topic
Location
Population of interest
“Inclusion Criteria” and “Exclusion Criteria” (Section 5.1 and 5.2) and
“Populations for Analyses” (Section 9.3)
Endpoints and variables
“Objectives and Endpoints” (Section 3)
handling of intercurrent events
Objectives and Endpoints” (Section 3) and additional details to be 
provided in the SAP
Population summary measures
“General Considerations” (Section 9.4.1)
9.4.1.2. Missing Data Imputation
While every effort will be made to minimize missing data, the missing data imputation methods 
described here will be used to provide a conservative approach for assessing efficacy endpoints 
when participants are permanently discontinued from study drug or otherwise have missing data.

Nonresponder imputation (NRI): For analysis of categorical efficacy and health outcomes 
variables, missing data will be imputed using an NRI method. Participants will be 
considered nonresponders for the NRI analysis if they do not meet the categorical 
efficacy criteria or have missing clinical efficacy data at a time point of interest.

The NRI method may be used when the estimand of interest uses the composite strategy35
for handling intercurrent events. In this strategy, participants with any intercurrent events 
that lead to the permanent discontinuation of assigned study treatment are defined to have 
failed treatment for all subsequent timepoints.

In addition, participants who were not adequately assessed to determine if they meet the 
clinical requirements for response at the time point of interest are also considered to have 
failed treatment.

Mixed-effect Model for Repeated Measures (MMRM): For continuous variables, the 
primary analysis will be MMRM with the missing at random assumption for handling 


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missing data. This analysis takes into account both missingness of data and the 
correlation of the repeated measurements. No additional imputation methods will be 
applied to the MMRM analysis. The MMRM method may be justified when the estimand 
of interest uses the hypothetical strategy35 for handling intercurrent events. In this 
strategy, the scientific question of interest is to assess the effect of study treatment in a 
hypothetical trial where all patients have complete data and continue to take study 
treatment without dropping out of the study or receiving rescue therapy.
For participants discontinuing study drug for any other reason, the last nonmissing postbaseline 
observation before discontinuation will be carried forward to the corresponding primary endpoint 
for evaluation. 
Additional missing data imputation methods, for example, modified baseline observation carried 
forward (mBOCF) may be considered as sensitivity analyses and will be described in the SAP. 
Using mBOCF imputation, participants who discontinue the study drug due to an AE or lack of 
efficacy will have their baseline observation carried forward to the corresponding primary 
endpoint for evaluation. Other missing data imputations methods, for example, based on multiple 
imputations (MI) or hybrid approaches (NRI and MI-based) may also be considered. Those 
sensitivity analyses and other additional methods of handling missing data or analyzing the data 
that may be required to satisfy regulatory needs or for other purposes will be specified in the 
SAP.
9.4.1.3. Adjustment for Multiple Comparisons
Adjustment for multiple comparisons will not be employed in the analysis for this study.
9.4.2. Treatment Group Comparability
9.4.2.1. Participant Disposition
The number of randomized participants will be summarized. Frequency counts and percentages 
of all participants who are randomized, complete the study, and those who discontinue the study 
drug or the study early will be presented. Reasons for discontinuing the study drug or the study 
will be summarized.
9.4.2.2. Participant Characteristics
Demographic data are collected and responded to demonstrate that the study population 
represents the target patient population. A summary of baseline participant characteristics, 
historical diagnoses, preexisting conditions, and prior therapies will be reported by treatment 
group using descriptive statistics. Other participant characteristics will be summarized by 
treatment group, or listed, as deemed appropriate.
9.4.2.3. Concomitant Therapy
Current concomitant therapy (reported after randomization) will be summarized by treatment 
group and will be presented by Anatomical Therapeutic Chemical (ATC) drug classes using the 
latest version of the WHO drug dictionary. Previous concomitant therapy (reported before 
randomization and after ICF) will be listed. 


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9.4.2.4. Treatment Compliance
Participants who are noncompliant with treatment will be listed by treatment group. The details 
of noncompliance will be defined in the SAP. No analyses are planned to assess treatment 
compliance.
9.4.3. Efficacy Analyses
9.4.3.1. Primary Analyses
The primary efficacy end point of clinical remission will be assessed using the MMS, a 9-point 
instrument that includes the SF, RB, and ES subscores of the Mayo Score (see Section 8.1).
At the screening visit, each participant will be asked to identify how many stools he or she had in 
a 24-hour period when in remission from UC. If the participant does not report that he or she has 
achieved remission, then he or she will be asked to identify the number of stools he or she had 
per day before initial onset of signs and symptoms of UC. The response to these questions will 
be used as the reference SF for the calculation of the Mayo SF subscore.
For the study visits associated with an endoscopy, the SF and RB subscores of the Mayo Score 
will be calculated from the patient-reported daily electronic diary data. Details regarding the 
calculation will be provided in the SAP. 
The primary endpoint analysis will utilize the CMH test as described in Section 9.4.1.
Additional analyses of the primary endpoint may be considered and details will be provided in 
the SAP.
9.4.3.2. Secondary Analyses
The secondary efficacy and health outcome endpoints will use the analysis methods described in 
Section 9.4.1.
9.4.4. Safety Analyses
Safety analyses will include AEs, SAEs, AESIs, C-SSRS, QIDS-SR16, vital signs, ECGs, and 
laboratory analytes, using the Safety Population data descriptively summarized by treatment 
group. Categorical safety measures will be summarized with incidence rates. Continuous safety 
measures will be summarized as mean change by visit. Exposure to study intervention will be 
calculated for each participant and summarized by treatment group.
Adverse events will be coded according to MedDRA and summarized by system organ class, 
preferred term, severity, and relationship to the study intervention. 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 experienced TEAEs, TEAEs by maximum 
severity, deaths, SAEs, TEAEs related to study intervention, discontinuations from the treatment 
due to an AE, and AESIs will be summarized. Treatment-emergent adverse events (all, by 


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Pr ot oc ol  J 1 P-M C -K F A H( b)
ma xi m u m se veri t y), S A Es i nclu d i n g deat hs, a n d A Es t hat lea d t o treat me nt disc o nti n uati on will 
be s u m marize d a n d a nal yze d b y Me d D R A S O C a n d preferre d ter m .
Treat me nt -relate d T E A Es ( T E A Es relate d t o st u d y i nter ve nt i on) are defi ne d as e ve nts t hat are 
i n dicate d b y t he i n vesti gat or o n t he eC R F t o be relate d t o treat me nt.
A d verse e ve nts of s pecial i nterest will be i de nt ifie d b y a sta n dar dize d Me d D R A q uer y ( S M Q) or 
a Lill y-defi ne d Me d D R A preferre d t er m listi n g.
F o ll ow- u p e m er ge nt A E s, S A Es i ncl u di n g deat hs, a n d A Es t hat lea d t o st u d y disc o nti nuat i on will 
be s u m marize d . All AEs, i ncl u di n g pre -e xist i n g c o n diti ons, will be liste d b y p arti ci pa nt , visit, 
preferre d ter m, treat me nt gr o u p, se verit y,  a n d relatio n s hi p t o t he treat me nt.
T he Fis her e xact test will be use d t o perf or m t he bet wee n- treat me nt gr o u p c o m paris o ns f or A Es, 
di sc o nti n uati ons, a n d ot her cate g orical safet y data. T he c ha n ge fr o m baseli ne i n c o nt i n u o us vital 
sig ns, p h ysical c haracterist ics, a n d ot her c o nti n u o us safet y varia bles, i ncl u di n g la b orat or y  
varia bles, will be s u m marize d visit a n d b y treat me nt. T he c ha n ge fr o m baseli ne t o last 
o bser vat i on val ue will be a nal yze d wit h A N O V A m o del wit h baseli ne as a c o variate. T he last 
n o n- missi n g o bser vat i on i n t he treat me nt peri o d will be use d as t he last o bser vati on.
9. 4. 5. P h ar m ac o ki netic/ P h ar m ac o d y n a mic A n al yses
Pl as ma c o nce ntratio ns of  L Y 3 4 7 1 8 5 1 will be liste d b y  time p oi nt usi n g descri pt i ve statistics. T he 
P K of L Y 3 4 7 1 8 5 1 ma y  als o be c haracterize d usi n g gra p hical e val uat i ons a n d mi xe d -effect 
( p o p ulatio n P K) m o deli n g a p pr oac hes via N O N M E M wit h t he N O N M E M s oftware. 
A nal yses of e x p os ure -res p o nse relati ons hi ps ma y be c o n d ucte d usi n g b ot h e x pl orat or y  gra p hical 
a p pr oac hes a n d m o del base d a p pr oac hes. F or e xa m ple, e x pl orat or y  gra p hical a nal ysis 
a p pr oac hes ma y c o nsist of gra p hs s h o wi n g t he perce n ta ges of  st u d y partici pa nts w h o ac hie ve 
cli nical res p o nse, cli nical re missi o n, a n d e n d osc o pic n or malizat i on at differe nt perce nt iles (f or 
e xa m ple, q uartiles) of e x p os ure of L Y 3 4 7 1 8 5 1 at Wee k 1 2. M o del-base d a nal yses ma y ut ilize 
p o p ul at i on e x p os ure -res p o nse l ogi stic re gressi on m o dels or l o n gi t u di nal e x p os ure res p o nse 
m o dels. 
A d dit i onal a nal yses ma y be c o n d ucte d if dee me d a p pr o priate. Data fr o m t his st u d y  ma y be 
c o m bi ne d wit h ot her st u d y  data, if a p pr o priate. F urt her details o n P K a n d P K/ P D a nal yses will 
be pr o vi de d i n t he P K/ P D a nal ysis pla n .
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1 1 1
9. 4. 7 . S u b gr o u p , S u p ple me nt al, a n d Ot her E x pl or at or y A n al yses
S u b gr o u p a nal yses
S u b gr o u p a nal yses will be c o n d ucte d f or t he pri mar y  e n d p oi nt a n d select sec o n dar y e n d p oi nts. 
S u b gr o u ps t o be e val uate d ma y i ncl u de 

se x

a ge cate g or y

b o d y  wei g ht

race

ge o gra p hi c re gio n

baseli ne disease se verit y a n d act i vity

d urati o n a n d l ocat i on of disease

pre vi o us s yste mic t hera p y

pre vi o us a d va nce d t hera p y, a n d 

c o nc o mita nt t hera p y for U C. 
If a n y gr o u p wit hi n t he s u b gr o u p is less t ha n 1 0 % of t he t otal p o p ulati on, o nl y  s u m maries of t he 
efficac y data will b e pr o vide d (t hat is, n o i nfe re ntial testi n g). A d diti onal s u b gr o u p a nal ysis will 
be defi ne d i n t he S A P
S u p pl e me ntal a nal yses
S u p pl e me ntal a nal yses will be perf or me d o n t he pri mar y e n d p oi nt usi n g a usi n g a l o gistic 
ra n d om effects mo d el  wit h tr e at me nt, baseli ne, visit, a n d visi t- b y-tr e at me nt i nteractio n. 
A d dit i onal a nal yses of sec o n dar y e nd p oi nts m a y be perf or me d usi n g t he sa me ra n d o m effects 
m o d el . A nal ysis details will be pr o vi de d i n t he S A P.
E x pl or at or y  a nal yses
E x pl or at or y  efficac y e n d p oi nt data, P D data, a n d bi o mar ker d ata will be a nal yze d as descri be d i n 
t he S A P.
9. 5. I nteri m A n al yses
A nal yses f or t he pri mar y data base loc k will  be c o n d ucte d w he n all part ici pa nts ha ve c o m p lete d 
t he I n d ucti o n Peri o d (t hat is, ha d c o m p lete d t he Wee k 1 2
visit ) or else ha ve disc o nt i n ue d st u dy 
treat me nt.
As n ote d i n Secti o n 4. 1 , se veral i nteri m a nal yses will be c o n d ucte d pri or t o t he pri mar y data base 
l oc k. T hese i nteri m a nal yses will be use d t o s u p p ort pla n ni n g act i vities ass ociate d wit h t his st u d y 
a n d t he L Y 3 4 7 1 8 5 1 cli nical de vel o p me nt pr o gra m. Si nce t he st u d y ma y ter mi nate earl y o nl y for 
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safety reasons, for futility, or for both, no adjustment of type I error will be performed. Interim 
futility details will be provided in the SAP. 
The following interim analyses may be considered.
Interim analysis to…
an interim analysis of
Will be conducted when…
Support planning activities, 
possibly including early termination
mITT population
Approximately 50 patients have completed 
12 weeks of treatment or discontinued 
treatment.
Support planning activities, 
possibly including early termination
mITT population
Approximately 100 patients have completed 
12 weeks of treatment or discontinued 
treatment.
Additional interim analyses may be performed only if deemed necessary by the sponsor to 
address critical questions.
An assessment of unblinded interim data will be conducted by an internal assessment committee
(IAC) with a limited number of prespecified team members who do not have direct site contact 
or data entry or validation responsibilities (see Appendix 1, Section 10.1.5). Only the IAC is
authorized to evaluate unblinded interim efficacy and safety analyses.
Prior to the interim or final database locks, a limited number of preidentified individuals may 
gain access to the unblinded data in order to initiate the 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. Unblinding details will be specified in the SAP
and Unblinding Plan. 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.
9.6. Data Monitoring Committee
Not applicable. An IAC will be used to conduct the interim analysis (see Section 9.5 and 
Appendix 1, Section 10.1.5).


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10. Supporting Documentation and Operational Considerations
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines

Applicable ICH GCP Guidelines, and

Applicable laws and regulations.
The protocol, protocol amendments and addenda, ICF, IB, and other relevant documents (for 
example, advertisements) must be submitted to an IRB/IEC by the investigator and reviewed and 
approved by the IRB/IEC before the study is initiated.
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
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, and

Providing oversight of study conduct for participants under their responsibility and 
adherence to requirements of 21 United States Code of Federal Regulations (CFR), ICH 
guidelines, the IRB/IEC, European regulation 536/2014 for clinical studies (if 
applicable), and all other applicable local regulations.
Investigator sites are compensated for participation in the study as detailed in the clinical trial 
agreement (CTA).
10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
one year after completion of the study.


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10.1.3. Informed Consent Process
The investigator or his or her representative will explain the nature of the study, including the 
risks and benefits, to the participant or his or her legally authorized representative and answer all 
questions regarding the study.
Participants must be informed that their participation is voluntary.
Participants or their legally authorized representatives will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, 
Health Insurance Portability and Accountability Act (HIPAA) requirements, where applicable, 
and the IRB/IEC or study center.
The 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 who are rescreened are required to sign a new ICF (see Section 5.4).
Participants must be reconsented to the most current version of the ICF during their participation 
in the study.
A copy of the ICF must be provided to the participant or the participant’s legally authorized 
representative and is kept on file.
10.1.4. Data Protection
Participants will be assigned a unique identifier by the sponsor. Any participant records, datasets, 
or tissue samples that are transferred to the sponsor will contain the identifier only. Participant 
names or any information which would make the participant identifiable will not be transferred.
The participant must be informed that his or her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for his or her data to be used as 
described in the informed consent.
The participant must be informed that his or her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities.
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
Internal Assessment Committee (IAC)
In addition to the safety reviews routinely performed by the blinded study team, an IAC will 
review the safety data in an unblinded fashion periodically or on an ad hoc basis during the study 
and will determine whether any changes (for example, dose reductions or other protocol 
modifications) should be made (see also Section 10.1.9).


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The IAC reviewing the safety data will be fully independent from the study team and will 
include, at a minimum, a Lilly medical physician, a statistician, and a representative from the 
Lilly Global Patient Safety organization. Details about IAC membership, purpose, 
responsibilities, and operation will be described in an IAC charter, which will be approved prior 
to the first unblinding.
Investigators and site personnel will receive information about interim analysis results only if 
they need to know for the safety of their study participants.
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.
Data
The sponsor provides access to all individual participant data collected during the trial, 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 United States and European Union 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, clinical study report, 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
Investigator responsibilities
All participant data relating to the study will be recorded on a printed or eCRF 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 eCRF. This documentation might include laboratory and diagnostic 
test reports, medical records, and clinical notes.
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents.
Data monitoring and management
Monitoring details describing strategy (for example, risk-based initiatives in operations and 
quality, such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities and requirements, including handling of noncompliance issues and 
monitoring techniques are provided in the Monitoring Plan.


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The sponsor or designee is responsible for the data management of this study, including quality 
checking of the data. The sponsor assumes accountability for actions delegated to other 
individuals (for example, contract research organizations).
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records retention and audits
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for the time period outlined in the CTA unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be transferred to 
another location or party without written notification to the sponsor.
In addition, the sponsor or its representatives will periodically check a sample of the participant 
data recorded against source documents at the study site. The study may be audited by the 
sponsor or its representatives, and/or regulatory agencies at any time. Investigators will be given 
notice before an audit occurs.
Data Capture System
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor.
An EDC system will be used in this study for the collection of eCRF data. The investigator 
maintains a separate source for the data entered by the investigator or designee into the sponsor-
provided EDC system. The investigator is responsible for the identification of any data to be 
considered source and for the confirmation that data reported are accurate and complete by 
signing the eCRF.
Additionally, some of the clinician-administered questionnaire data will be collected by the 
authorized site personnel via a paper source document and will be transcribed by the authorized 
site personnel into the EDC system. See the SoA for scales administered via paper.
Additionally, eCOA data (patient-reported outcome and clinician-administered questionnaires) 
will be directly recorded by the participant and authorized study personnel into an instrument 
(for example, tablet and/or a web-based collection system). The eCOA data will serve as the 
source documentation, and the investigator does not maintain a separate, written or electronic 
record of these data. See Section 1.3 for scales administered electronically.
Data collected via the sponsor-provided data capture systems will be stored at third parties. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture systems. Prior to decommissioning, the investigator will receive an archival 
copy of pertinent data for retention.
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
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and retention. Data will subsequently be transferred from the central vendor to the sponsor’s data 
warehouse.
Data from complaint forms submitted to the sponsor will be encoded and stored in the global 
product complaint management system.
10.1.8. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents, or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on the 
study. Also, current medical records must be available.
The definition of what constitutes source data can be found in Section 10.1.7.
10.1.9. Study and Site Start and Closure
The study start date is the date on which the clinical study is open for recruitment of participants.
The study or a study site will be discontinued if the sponsor or its designee judges it necessary 
for medical, safety, regulatory, or other reasons consistent with applicable laws, regulations, and 
GCP.
Closure of study sites
Study sites will be closed upon study completion. A study site is considered closed when all 
required documents and study supplies have been collected and a study-site closure visit has 
been performed.
The investigator may initiate study-site closure at any time, provided a reasonable cause exists 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include, but are 
not limited to,

failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines

inadequate recruitment of participants by the investigator, and

discontinuation of further study intervention development.
Study stopping rules
The IAC will convene to evaluate unblinded safety data if

5 or more participants experience TEAEs in the same SOC or 3 or more participants 
experience a TEAE of CRS, and
o
these TEAEs are judged as either serious or severe, and
o
these TEAEs are related to blinded study treatment.


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1 1 8
St u d y  e nr oll me nt a n d/ or f urt her d osi n g ma y be st o p pe d, pe n di n g t he decisi on of t he I A C 
( Sectio n 9. 5 a n d Secti o n 1 0. 1. 5 ). If t he st u d y is n ot st o p pe d, t he I A C will meet peri o dicall y. 
Details are pr o vi de d i n t he I A C c harter.
I nteri m a nal yses will be perf or me d as descri be d i n Secti o n 9. 5 . Details will be pr o vi de d i n t he 
S A P. If t he st u d y  is dee me d f utile, st u d y e nr oll me nt a n d/ or f urt her d osi n g ma y be st o p pe d.
If t he st u d y is pre mat urel y ter mi nate d or s us pe n de d, t he s p o ns or s hall pr o m ptl y i nf or m t he 
i n vesti gat ors, t he I E Cs/I R Bs, t he re g ulat or y a ut h orities, a n d a n y c o ntract researc h or ga nizati ons 
use d i n t he st u d y  of t he reas o n f or ter mi nati on or s us p e nsio n , as s pecifie d b y t he a p plica ble 
re g ulat or y r e q uire me nts. T he i n vesti gat or s hall pr o m ptl y i nf or m t he partici pa nt a n d ass ure 
a p pr o priate partici pa nt t hera p y a n d/ or f ollo w - u p.
1 0. 1. 1 0. P u blic ati o n P olic y
I n acc or da nce wit h t he s p o ns or’s p u blicati o n p olic y, t he res ults of t his st u d y will be s u b mitte d 
f or p u blicati on b y a peer -re vie we d j o ur nal.
1 0. 1. 1 1. I n vesti g at or I nf or m ati o n
P h ysicia ns wit h a s pecialt y i n gastr oe nter ol o g y will p artici pate as i n vesti gat ors i n t his cli nical 
trial.
1 0. 1. 1 2. L o n g -Ter m S a m p le Rete nti o n
S a m ple rete nti o n e na bles use of ne w tec h n o l ogi es, res p o nse t o re g ulat or y q uesti ons, a n d 
i n vesti gati on of varia ble res p o nses t hat ma y  not be o bser ve d u nt il later i n t he de vel o p me nt of  
L Y 3 4 7 1 8 5 1 or after L Y 3 4 7 1 8 5 1 bec o mes c o m mer ciall y a vaila ble .
T he f o ll owi n g ta bl e lists t he ma xi m u m rete ntio n p eri o d f or s a m ple t y pes.
T he rete nti o n peri o d be gi ns after t he last partici pa nt visit f or t he st u d y .
T he m a xi m u m rete nti on ti mes ma y  be s h orter, if s pecifie d i n l ocal re g ulat i ons a n d/ or if 
E R Bs/I R Bs i m p ose s h orter ti me li mits, or b y decisio n  of t he s p o ns or.
A n y sa m ples re mai ni n g after t he s pecifie d rete nt i on peri o d will be destr o y e d.
T he sa m ple rete nti o n facilit y will be selecte d b y t he s p o ns or or its desi g nee.
S a m ple T y pe
C ust o di a n
Rete nti o n Peri o d after L ast P artici p a nt Visit
P har mac o ki netics
S p o ns or or desi g nee
2 years
S p o ns or or desi g nee
U p t o 1 5 years
P har mac o ge netics
S p o ns or or desi g nee
U p t o 1 5 years
S p o ns or or desi g nee
U p t o 1 5 years
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10.2. Appendix 2: Clinical Laboratory Tests
10.2.1. Clinical Laboratory Tests
The clinical laboratory tests detailed here will be performed by a central laboratory or by a local 
laboratory as specified in the tables.
If laboratory tests are done to obtain laboratory results with an intent to resume the study drug 
after a temporary interruption of study drug, the samples should be assayed centrally.
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or as required by local regulations.
Protocol-specific requirements for the inclusion or exclusion of participants are specified in 
Section 5.
Pregnancy testing is described in the SoA, in Section 8.2.5.1, and in the table in this section.
Investigators must document their review of the laboratory safety results.
Laboratory test results that could unblind the study will not be reported to investigative sites or 
other blinded personnel.
Notes
Hematology
Assayed by Lilly-designated laboratory.
Hemoglobin
Hematocrit
Erythrocyte count (red blood cells [RBC])
Mean cell volume
Mean cell hemoglobin
Mean cell hemoglobin concentration
Leukocytes (white blood cells [WBC])
Absolute count of:
    Neutrophils, segmented
    Neutrophils, juvenile (bands)
    Lymphocytes
    Monocytes
    Eosinophils
    Basophils
Platelets
Cell morphology (RBC and WBC)


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Notes
Clinical Chemistry
Assayed by Lilly-designated laboratory.
Sodium
Potassium
Chloride
Bicarbonate
Total bilirubin (TBL)
Direct bilirubin
Alkaline phosphatase (ALP)
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Gamma-glutamyl transferase (GGT)
Blood urea nitrogen (BUN)
Creatinine
Estimated glomerular filtration rate 
(eGFR)
See calculations below, in this appendix.
Creatine kinase (CK)
Uric acid
Total protein
Albumin
Calcium
Glucose
Notes
Lipid Panel
Assayed by Lilly-designated laboratory. Participant should 
not eat or drink anything except water for 12 hours before 
the test. If participant is nonfasting at time of collection, 
this is not a protocol deviation.
Low-density lipoprotein (LDL)
High-density lipoprotein (HDL)
Cholesterol (total)
Triglycerides


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N otes
Uri n al ysis
Assa y e d b y Lill y-desi g nate d la b orat or y .
S pecific gra vit y
p H
Pr otei n
Gl uc ose
Ket o nes
Bilir u bi n
Ur o bili n o ge n
Bl o o d
Nitrite
Ur i ne le u k oc yte esterase
Micr osc o pic e xa mi nati o n of se di me nt
N otes
H or m o nes (fe m ales)
Pre g na nc y test – seru m
Assa y e d b y Lill y-desi g nate d la b orat or y .
T o be perf or me d o nl y o n w o me n of c hil d beari n g p ote ntial
a n d w o me n wit h hist or y of t u bal li gati o n .
Pre g na nc y test – uri ne
E val uate d l ocall y.
T o be perf or me d o nl y o n w o me n of c hil d beari n g p ote ntial
a n d w o me n wit h hist or y of t u bal li gati o n . 
Res ult m ust be ne gati ve bef ore d osi n g at eac h d osi n g visit.
F ollicle -sti m ulati n g h or m o ne ( F S H)
Assa y e d b y Lill y-desi g nate d la b orat or y
O pti o nal, perf or me d t o c o nfir m p ost me n o pa usal stat us . 
N otes
A d diti o n al Testi n g
Assa y e d b y Lill y-desi g nate d la b orat or y.
Res ults will n ot be pr o vi de d t o t he i n vesti gati ve sites.
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1 2 2
N otes
T B , HI V, a n d He p atitis Ser ol o g y
T u berc ul osis ( T B) test :
T B test base d o n l ocal sta n dar d of care
     Q ua nti F E R O N ®- T B G o ld test
Assa y e d b y Lill y-desi g nate d la b orat or y .
     T-S P O T ® . T B
E val uate d l ocall y .
L ocal la bor at or y m ust be q ualifie d b y l ocal re g ulati o ns .
     Tu berc uli n s ki n test (T S T )
L ocal testi n g.
L ocal la bor at or y m ust be q ualifie d b y l ocal re g ulati o ns .
H u ma n i m m u n o deficie nc y vir us ( HI V)
Assa y e d b y Lill y-desi g nate d la b orat or y .
He patitis C vir us ( H C V) testi n g:
Assa y e d b y Lill y-desi g nate d la b orat or y .
     He patitis C a nti b o d y
     H C V R N A
He patitis B vir us ( H B V) testi n g:
Assa y e d b y Lill y-desi g nate d la b orat or y .
      He patitis B s urface a nti ge n (H Bs A g )
      He patitis B c ore a nti b o d y (anti -H Bc )
     H B V D N A
Perf or me d o nl y f or partici pa nts w h o test p ositi ve f or 
a nti -H Bc.  
N otes
P h ar m ac o ki netics ( P K) S a m ples
Assa y e d b y Lill y-desi g nate d la b orat or y .
Res ults will n ot be pr o vi de d t o t he i n vesti gati ve sites .
L Y 3 4 7 1 8 5 1 c o nce ntrati o n
N otes
Assa y e d b y Lill y-desi g nate d la b orat or y .
Res ults will n ot be pr o vi de d t o t he i n vesti gati ve sites .
N otes
Fl o w C yt o metr y
Assa y e d b y Lill y -desi g nate d la b orat or y .
Res ults will n ot be pr o vi de d t o t he i n vesti gati ve sites .
L y m p h oc y t e su bsets - T re g ulat o r y cells
T- cell s u bsets
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
1 2 3
N otes
G e netics S a m ples
Assa y e d b y Lill y-desi g nate d la b orat or y .
Res ults will n ot be pr o vi de d t o t he i n vesti gati ve sites.
G e netics sa m ple
N otes
Assa y e d b y Lill y-desi g nate d la b orat or y .
Res ults will n ot be pr o vi de d t o t he i n vesti gati ve sites .
E n d osc o pic bi o ps y sa m ple c ollecti o n
N otes
St o ol S a m ples
Assa y e d b y Lill y-desi g nate d la b orat or y .
St o ol c ult ure
Cl ostri di u m difficile testi n g
C o nfir me d b y a test f or C. difficile t o xi n ge ne e x pressi o n.
Res ults will n ot be pr o vi de d t o t he i n vesti gati ve sites .
Cli nic al L a b or at or y C alc ul ati o ns
e G F R ( M D R D)
● F or creati ni ne res ults re p orte d i n c o n ve nt i onal u nits ( m g/ d L):
G F R ( m L / mi n/ 1. 7 3 m²) = 1 7 5 × ( Scr)-1. 1 5 4 × ( A ge) -0. 2 0 3 × ( 0. 7 4 2 if fe male) × ( 1. 2 1 2 if Africa n 
A merica n) 
●F o r creati ni ne res ults re p orte d i n SI u nits ( p m ol/L):
G F R ( m L/ mi n/ 1. 7 3 m²) = 1 7 5 × ( S cr/ 8 8. 4)-1. 1 5 4 × ( A ge) -0. 2 0 3 × ( 0. 7 4 2 if fe male) × ( 1. 2 1 2 if 
Afr ica n America n) 
C CI
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
1 2 4
1 0. 2. 2. L a b or at or y Tests t o be O bt ai ne d at Ti me of a S yste mic H y perse nsiti vit y E ve nt
S el ecte d tests ma y be o btai ne d i n t he e ve nt of a na p h yla xis or s yste mic aller gic/ h y perse nsiti vity 
reactio ns. T he sa m ples s h o ul d be c ollecte d as cl ose as p ossi ble t o t he o nset of t he e ve nt.
H y perse nsiti vit y Tests a
L Y c o nce ntrati o n ( P K)
N- met h y l hista mi ne
C o m ple me nts
C y t o ki ne pa nel
A b bre viati o n: L Y = L Y 3 4 7 1 8 5 1; N M H = N -met h y l hista mi ne; P K = p har mac o ki netics.
a
Assa y e d b y Lill y-desi g nate d la b orat or y. Res ults will n ot be pr o vi de d t o t he i n vesti gati ve sites.
C CI
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
1 2 5
1 0. 3. A p pe n di x 3: A d verse E ve nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, 
E v al u ati n g, F oll o w u p a n d Re p orti n g
1 0. 3. 1. Defi niti o n o f A E
A E Defi niti o n
A n A E i s a n y u nt o war d me dical occ urre nce i n a patie nt or cli nical st u d y p artici pa nt, te mp orall y 
ass ociat e d wit h t he use of st u d y int er ve nt i on, w het her or n ot c o nsi dere d relate d t o t he st u d y  
i nter ve nt i on.
N O T E: A n A E ca n t heref ore be a n y u nf a v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n a b n or mal 
la b orat or y fi n di n g), s y m pt o m, or disease ( ne w or e xacer bate d) te m p orall y ass ociate d wit h t he use 
of  st u d y int er ve nt i on.
E ve nts Meeti n g t he A E Defi niti o n

A n y a b n or mal la b orat or y  test res ults ( he mat olo g y , cli nical c he mistr y, or urinal ysis) or ot her 
safety assess me nts (f or e xa m ple, E C G, ra di o l ogi c al sca ns, vit al si g ns meas ure me nts), 
i ncl u di n g t h ose t hat w orse n fr om baseli ne, c o nsi dere d cli nicall y si g nifica nt i n t he me dical 
a n d scie nt ific j u d g me nt of t he i nvest i gat or (t hat is, n ot relate d t o pr o gressi o n of u n derl yi n g 
di sease).

E xacer bat i on of a c hr o nic or i nter mitte nt pre -e xist i n g c o n diti on, i ncl u di n g a n i ncrease i n 
fre q ue nc y a nd/ or i nt e nsit y of t he c o n ditio n.

Ne w c o n dit i ons detecte d or dia g n ose d after st u d y i nter ve nti on a d mi nistrati o n , e ve n t h o u g h 
t he y ma y ha ve bee n prese nt bef ore t he start of t he st u d y.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g -dr u g i nteracti o n.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o ver d ose of eit her st u d y int er ve nt i on 
or a c o nc o mita nt me dicat i on. O ver d ose , per se , will n ot be re p orte d as a n A E or S A E u nless 
it is a n i nte nti onal o ver d ose ta ke n wit h p ossi ble s uici dal/self -har mi n g i nte nt . S uc h o ver d oses 
s h o uld be re p orte d re gar dless of se q uelae.
“ Lac k of efficac y” or “fail ure of e x pecte d p har mac ol o gical act i on” , per se , will n ot be re p orte d 
as a n A E or S A E. S uc h i nsta nces will be ca pt ure d i n t he efficac y assess me nts. H o we ver, t he 
sig ns, s y m pt o m s, a n d/ or cli nical se q uelae res ult i n g fr om lac k of efficac y will be re p orte d as A E 
or S A E , if t he y f ulfill t he defi niti on o f a n A E or S A E.
E ve nts N ot Meeti n g t he A E Defi niti o n

A n y cli nicall y  sig nifica nt a b n or mal la b orat or y  fi n di n gs or ot her a b n or mal safety assess me nts 
w hic h are ass ociate d wit h t he u n derl yi n g disease, u nless j u d ge d b y t he i n vesti gat or t o be 
m o re se vere t ha n e x pecte d f or t he partici pa nt’s c o n diti on.
 

T he disease/ dis or der bei n g st u die d or e x pecte d pr o gressi o n, si g ns, or s y m pt o m s of t he 
di sease/ dis or der bei n g st u die d, u nless m ore se vere t ha n e x pecte d f or t he partici pa nt’s 
c o n ditio n.
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
Medical or surgical procedure (for example, endoscopy or 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 diseases or conditions present or detected 
at the start of the study that do not worsen.
10.3.2. Definition of SAE
Note: If an event is not an AE per definition above, then it cannot be an SAE, even if serious 
conditions are met (for example, hospitalization for signs/symptoms of the disease under study or
death due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
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 for 
observation and/or treatment that would not have been appropriate in the physician’s office or 
outpatient 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/incapacity
The term disability means a substantial disruption of a person’s ability to conduct 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/birth defect
f.
Other situations:
Medical or scientific judgment should be exercised 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.


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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. Recording and Follow-Up of AE and/or SAE
AE and SAE Recording
When an AE/SAE 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.
The investigator will then record all relevant AE/SAE information in the CRF.
It is not acceptable for the investigator to send photocopies of the participant’s medical records 
to the sponsor or designee in lieu of completion of the AE/SAE CRF page.
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/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: An event that is easily tolerated by the participant, causing minimal discomfort and 
not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. 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.
Note: 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.
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.
The investigator will use clinical judgment to determine the relationship.


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Alternative causes, such as underlying diseases, 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 and/or Product Information, for marketed products, in 
his/her 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 the 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 the sponsor or designee.
The investigator may change his or her 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 the sponsor or designee with a copy of any post-mortem findings, 
including histopathology.
New or updated information will be recorded in the originally completed CRF.
The investigator will submit any updated SAE data to sponsor or designee within 24 hours of 
receipt of the information.
10.3.4. 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 paper SAE data collection tool
(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 paper SAE form or to the sponsor by telephone.


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Contacts for SAE reporting can be found in site training documents.
SAE Reporting via Paper CRF
Facsimile transmission of the SAE paper CRF 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 in site training documents.


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


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o
At least 55 years of age, not on hormone therapy, having at least 12 months of 
spontaneous amenorrhea
o
At least 55 years of age with a diagnosis of menopause prior to starting hormone 
replacement therapy.
10.4.2. Contraception
Females
Women of child-bearing potential
Women of child-bearing potential who are abstinent (if this is complete abstinence, as their 
preferred and usual lifestyle) or in a same sex relationship (as part of their preferred and usual 
lifestyle) must agree to either remain abstinent or stay in a same sex relationship without sexual 
relationships with males. Periodic abstinence (for example, calendar, ovulation, symptothermal, 
or post-ovulation methods), declaration of abstinence just for the duration of a trial, and 
withdrawal are not acceptable methods of contraception.
Otherwise, women of child-bearing potential participating must agree to use 2 forms of effective 
contraception, where at least 1 form is highly effective (less than 1% failure rate), for the entirety 
of the study. Contraception must continue following completion of study drug administration for 
12 weeks.

Women of child-bearing potential participating must test negative for pregnancy prior to 
initiation of treatment as indicated by a negative serum pregnancy test at the screening 
visit followed by a negative urine pregnancy test within 24 hours prior to first exposure to 
study drug.

Two forms of effective contraception, where at least 1 form is highly effective (such as 
combination oral contraceptives, implanted contraceptives, or intrauterine devices), will 
be used. Effective contraception (such as male or female condoms with spermicide, 
diaphragms with spermicide, or cervical sponges) may be used as the second therapy. 
Barrier protection methods without concomitant use of a spermicide are not a reliable or 
acceptable method. Thus, each barrier method must include use of a spermicide (that is, 
condom with spermicide, diaphragm with spermicide, female condom with spermicide). 
It should be noted that the use of male and female condoms as a double-barrier method is 
not considered acceptable due to the high failure rate when these methods are combined.
Women not of child-bearing potential
Women who are not-WOCBP may participate in the study, if they meet all study entry criteria. 
For such women, there are no contraception requirements.
Males
No male contraception is required except in compliance with specific local government study 
requirements.


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10.4.3. Collection of Pregnancy Information
Male participants with partners who become pregnant
The investigator will attempt to collect pregnancy information on any male participant’s female 
partner who becomes pregnant while the male participant is in this study. This applies only to 
male participants who receive study intervention.
After obtaining the necessary signed informed consent from the pregnant female partner directly, 
the investigator will record pregnancy information on the appropriate form and submit it to the 
sponsor within 24 hours of learning of the partner’s pregnancy. The female partner will be 
followed to determine the outcome of the pregnancy. Information on the status of the mother and 
child will be forwarded to the sponsor. Generally, the follow-up will be no longer than 6 to 8 
weeks following the estimated delivery date. Any termination of the pregnancy will be reported 
regardless of 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 6 to 8 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 less than 20 weeks gestational age) or still birth (occurring 
at 20 weeks or greater gestational age) is always considered to be an SAE and will be reported as 
such.
Any post-study pregnancy-related SAE considered reasonably related to the study intervention 
by the investigator will be reported to the sponsor as described in Section 8.3.4. While the 
investigator is not obligated to actively seek this information in former study participants, he or 
she may learn of an SAE through spontaneous reporting.
Any female participant who becomes pregnant while participating in the study will discontinue 
study intervention and be withdrawn from the study. If the participant is discontinued from the 
study intervention, follow the standard discontinuation process and continue directly to the study 
follow-up phase. The follow-up on the pregnancy outcome should continue independent of 
intervention or study discontinuation.


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10.5. Appendix 5: Liver Safety: Hepatic Monitoring Tests
See Section 8.2.9 for guidance on appropriate test selection.
The Lilly-designated central laboratory must complete the analysis of all selected testing except 
for microbiology testing.
Local testing may be performed in addition to central testing when necessary for immediate 
participant management.
Results will be reported if a validated test or calculation is available.
Hepatic Evaluation Testing
Hematology
Clinical Chemistry
Hemoglobin
Total bilirubin
Hematocrit
Direct bilirubin
Erythrocytes (RBCs - red blood cells)
Alkaline phosphatase (ALP)
Leukocytes (WBCs - white blood cells)
Alanine aminotransferase (ALT)
Differential:
Aspartate aminotransferase (AST)
    Neutrophils, segmented
Gamma-glutamyl transferase (GGT)
    Lymphocytes
Creatine kinase (CK)
    Monocytes
Other Chemistry
    Basophils
Acetaminophen
    Eosinophils
Acetaminophen protein adducts
Platelets
Alkaline phosphatase isoenzymes
Cell morphology (RBC and WBC)
Ceruloplasmin
Coagulation
Copper
Ethyl alcohol (EtOH)
Prothrombin time, INR (PT-INR)
Haptoglobin
Serology
Immunoglobulin A (IgA; quantitative)
Hepatitis A virus (HAV) testing:
Immunoglobulin G (IgG; quantitative)
    HAV total antibody
Immunoglobulin M (IgM; quantitative)
    HAV IgM antibody
Phosphatidylethanol (PEth)
Hepatis B virus (HBV) testing:
Urine Chemistry
    Hepatitis B surface antigen (HBsAg)
Drug screen
    Hepatitis B surface antibody (anti-HBs)
Ethyl glucuronide (EtG)
    Hepatitis B core total antibody (anti-HBc)
Other Serology
    Hepatitis B core IgM antibody
Anti-nuclear antibody (ANA)
    Hepatitis B core IgG antibody
Anti-smooth muscle antibody (ASMA)a
    HBV DNAd
Anti-actin antibodyb
Hepatis C virus (HCV) testing:
Epstein-Barr virus (EBV) testing:
    HCV antibody
    EBV antibody
    HCV RNAd
    EBV DNAd
Hepatitis D virus (HDV) testing:
Cytomegalovirus (CMV) testing:
    HDV antibody
    CMV antibody


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Hepatitis E virus (HEV) testing:
    CMV DNAd
    HEV IgG antibody
Herpes simplex virus (HSV) testing:
    HEV IgM antibody
    HSV (Type 1 and 2) antibody 
    HEV RNAd
    HSV (Type 1 and 2) DNAd
Microbiologyc
Liver kidney microsomal type 1 (LKM-1) antibody
Culture:
    Blood
    Urine
a
Not required if anti-actin antibody is tested.
b
Not required if anti-smooth muscle antibody (ASMA) is tested.
c
Assayed ONLY by investigator-designated local laboratory; no central testing available.
d
Reflex/confirmation dependent on regulatory requirements, testing availability, or both.


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10.6. Appendix 6: Examples of Infections That May Be Considered 
Opportunistic in the Setting of Biologic Therapy
The following table lists examples of infections that may be considered opportunistic in the 
setting of biologic therapy (adapted from Winthrop et al.16). This table is provided to aid the 
investigator in recognizing such infections. This list is not exhaustive. Infections will be 
categorized by Lilly as opportunistic according to Opportunistic Infections and Biologic 
Therapies in Immune-Mediated Inflammatory Diseases: Consensus Recommendations for 
Infection Reporting during Clinical Trials and Postmarketing Surveillance by Winthrop et al.16
Examples of Infections That May Be Considered Opportunistic in the Setting of Biologic 
Therapy
Bacterial
Bartonellosis (disseminated disease only)
Campylobacteriosis (invasive disease only)
Legionellosis
Listeriosis (invasive disease only)
Nocardiosis
Tuberculosis
Non-tuberculous mycobacterial disease
Salmonellosis (invasive disease only)
Shigellosis (invasive disease only)
Vibriosis (invasive disease due to Vibrio vulnificus)
Viral
BK virus disease including polyomavirus-associated nephropathy
Cytomegalovirus disease
Hepatitis B virus reactivation
Hepatitis C virus progression
Herpes simplex (invasive disease only)
Herpes zoster (any form)
Post-transplant lymphoproliferative disorder (Epstein-Barr virus)
Progressive multifocal leukoencephalopathy (PML), John Cunningham (JC) virus
Fungal
Aspergillosis (invasive disease only)
Blastomycosis
Candidiasis (invasive disease or oropharyngeal, esophageal. Not isolated lingual.)


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Coccidioidomycosis
Cryptococcosis
Histoplasmosis
Paracoccidioides infections
Penicilliosis
Pneumocystosis
Sporotrichosis
Other invasive molds: Mucormycosis (zygomycosis) (Rhizopus, Mucor, and Lichtheimia), 
Scedosporium/Pseudallescheria boydii, Fusarium
Parasitic
Leishmaniasis (visceral only)
Strongyloidiasis (hyperinfection syndrome or disseminated disease)
Microsporidiosis
Toxoplasmosis
Trypanosoma cruzi infection (Chagas’ disease progression) (disseminated disease only)
Cryptosporidiosis (chronic disease only)
Source: adapted from Winthrop et al.16


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10.7 Appendix 7: Prohibited Medications
This section outlines medications that are prohibited during the treatment phase of the study.
These prohibitions include windows for washout of medications prohibited prior to the screening 
endoscopy, if applicable.
After a patient discontinues study drug and completes the ETV, use of the medications listed in 
this appendix is allowed, at discretion of the investigator.
Drug Class
Prohibited Medication Restrictions
Anti-TNF antibodies (for example, infliximab, adalimumab,
or golimumab)
Discontinue at least 4 weeks prior to screening 
endoscopy and prohibited throughout duration of 
study.
Anti-integrin antibodies (for example, vedolizumab)
Discontinue at least 12 weeks prior to screening 
endoscopy and prohibited throughout duration of 
study.
Anti-IL12p40 antibodies (for example, ustekinumab 
[Stelara®]) or anti-IL-23p19 antibodies (for example, 
mirikizumab [LY3074828], risankizumab [BI-655066], 
brazikumab [MEDI-2070], guselkumab [CNTO1959], 
tildrakizumab [MK-3222]) for any indication, including 
investigational use
Discontinue at least 4 weeks prior to screening 
endoscopy and prohibited throughout duration of 
study.
Agents depleting B or T cells (for example, rituximab, 
alemtuzumab, or visilizumab)
Discontinue at least 12 months prior to baseline. 
Participants remain excluded, if evidence of 
persistent targeted lymphocyte depletion at the 
time of screening endoscopy.
Immunomodulatory medications, including oral 
cyclosporine, IV cyclosporine, tacrolimus, mycophenolate 
mofetil, thalidomide, or JAK inhibitors (for example, 
tofacitinib or baricitinib)
Discontinue at least 2 weeks prior to screening 
endoscopy and prohibited throughout duration of 
study.
Rectally administered 5-ASA therapies (enemas or 
suppositories)
Discontinue at least 2 weeks prior to screening 
endoscopy and prohibited throughout duration of 
study.
Rectally administered investigational preparations for UC 
such as arsenic preparations
Discontinue at least 4 weeks prior to screening 
endoscopy and prohibited throughout duration of 
study.
Rectally administered corticosteroids (enemas or 
suppositories or foam applications)
Discontinue at least 2 weeks prior to screening 
endoscopy and prohibited throughout duration of 
study.
IV corticosteroids
Discontinue at least 2 weeks prior to screening 
endoscopy. A course of IV corticosteroids is 
prohibited throughout duration of study.


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Drug Class
Prohibited Medication Restrictions
Systemic corticosteroids for non-UC indications (oral or IV)
Participants requiring systemic corticosteroids 
for non-UC indications (except corticosteroids to 
treat adrenal insufficiency) are excluded. Locally 
administered corticosteroids (for example, 
inhaled, intranasal, intra-articular, or topical) are 
allowed.
Oral budesonide standard formulation (that is, not the oral 
budesonide extended release tablet formulation [budesonide 
MMX])
Discontinue at least 2 weeks prior to screening 
endoscopy and prohibited throughout duration of 
study.
Any investigational therapy (biologic or nonbiologic) not 
otherwise mentioned in this table
Biologic: Discontinue at least 8 weeks, or 
5 half-lives, whichever is longer, prior to 
screening endoscopy and prohibited 
throughout duration of study.
Nonbiologic: Discontinue at least 4 weeks, or 
5 half-lives, whichever is longer, prior to 
screening endoscopy and prohibited 
throughout duration of study.
Interferon therapy
Discontinue at least 8 weeks prior to screening 
endoscopy and prohibited throughout duration of 
study.
Leukocyte apheresis (leukapheresis, for example, 
Adacolumn)
Discontinue at least 3 weeks prior to screening 
endoscopy.
Bacillus Calmette-Guerin (BCG) vaccine
Last vaccination (if any) given at least 12 months 
prior to baseline. BCG vaccination is prohibited 
throughout the duration of the study and for 20 
weeks after discontinuation of study drug.
Live attenuated vaccines
Last vaccination (if any) given at least 3 months 
prior to baseline. Live attenuated vaccines are 
prohibited throughout the duration of the study 
and for 20 weeks after discontinuation of study 
drug.
Abbreviations: 5-ASA = 5-aminosalicyclic acid; IL = interleukin; IV = intravenous; JAK = Janus Kinase; 
TNF = tumor necrosis factor; UC = ulcerative colitis.


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10.8. Appendix 8: Permitted Medications with Dose Stabilization
Drug Class
Dose Stabilization Guidance
Oral 5-ASAs for UC (for example, mesalamine, 
balsalazide, olsalazine and sulfasalazine)
The prescribed dose must have been stable for at least 
2 weeks prior to the screening endoscopy, with stable 
dose encouraged during the study.
Oral corticosteroids for UC (prednisone ≤20 mg/day or 
equivalent, budesonide MMX 9 mg/day, or 
beclomethasone dipropionate [gastro-resistant 
prolonged-release tablet] 5 mg/day)
Prescribed dose must have been stable for at least 2 
weeks before screening endoscopy. See Section 6.5
for instructions on tapering of oral corticosteroid 
therapy.
Corticosteroids for non-UC indications: corticosteroids 
to treat adrenal insufficiency, or locally administered 
corticosteroids (for example, inhaled, intranasal, intra-
articular, or topical)
May continue corticosteroids to treat adrenal 
insufficiency or locally administered corticosteroids 
during study with stable dose encouraged.
Immunomodulators (for example, AZA, 6-MP, or 
methotrexate)
Prescribed at stable dose for at least 8 weeks before 
screening endoscopy; doses should remain stable 
throughout study unless medication is discontinued 
due to a toxicity related to the medication.
Antidiarrheals (for example, loperamide or
diphenoxylate with atropine)
May continue during study with stable doses 
encouraged.
Low-dose or baby aspirin (75 to 162.5 mg)
Daily use for cardiovascular prophylaxis permitted.
Non-live (killed, inactivated, or subunit) vaccines
Allowed during the study. The efficacy of non-live 
vaccinations with concomitant LY3471851 treatment
is unknown.
Abbreviations: 5-ASA = 5-aminosalicyclic acid; 6-MP = 6-mercaptopurine; AZA = azathioprine; UC = ulcerative 
colitis.


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10.9. Appendix 9: Mayo Scoring System for the Assessment of Ulcerative 
Colitis Activity
Stool Frequency Subscore
Score
Normal number of stools for subject
0
1 to 2 stools more than normal
1
3 to 4 stools more than normal
2
5 or more stools than normal
3
Rectal Bleeding Subscore
Score
No blood seen
0
Streaks of blood with stool less than half of the time
1
Obvious blood (more than just streaks) or streaks of blood with stool most of the time
2
Blood alone passed
3
Endoscopic Subscore
Score
Normal or inactive disease
0
Mild disease (erythema, decreased vascular pattern)
1
Moderate disease (marked erythema, absent vascular pattern, friability, erosions)
2
Severe disease (spontaneous bleeding, ulceration)
3
Physician’s Global Assessment
Score
Normal
0
Mild disease
1
Moderate disease
2
Severe disease
3
Mayo Score = Stool Frequency + Rectal Bleeding + Endoscopic Subscore + Physician's Global Assessment
Note: The Mayo score ranges from 0 to 12, with higher scores indicating more severe disease. Modified Mayo score 
excludes the Physician’s Global Assessment and ranges from 0 to 9. Composite stool frequency and rectal bleeding 
score ranges from 0 to 6. The original description of the Mayo score included friability in the definition of an 
endoscopic subscore of 1. Consistent with current clinical practice and regulatory guidance, this study excludes 
friability from the definition of an endoscopic subscore of 1. Stool frequency reports the number of stools in a 
24-hour period, relative to the normal number of stools for that patient. The reference “normal” stool frequency for 
that patient will be recorded electronically at the screening visit. The Normal SF refers to when the patient was in 
remission or, if the patient has never achieved remission, the reported stool frequency before initial onset of signs 
and symptoms of UC. Remission refers to a period of time since being diagnosed with UC when the patient is not 
experiencing any signs or symptoms relating to UC. This period of time may last a few weeks or a few months or 
may even last several years. The patient will record this electronically as source data at the screening study visit.
Source: Adapted from Schroeder et al.17 and Scherl et al.20


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10.10. Appendix 10: Geboes Scoring for the Assessment of Histological 
Activity
Subgrades
Scoring
Grade 0 
Structural (architectural change)
0.0    No abnormality
0.1    Mild abnormality
0.2    Mild or moderate diffuse or multifocal abnormalities
0.3    Severe diffuse or multifocal abnormalities
Grade 1 
Chronic inflammatory infiltrate
1.0    No increase
1.1    Mild but unequivocal increase
1.2    Moderate increase
1.3    Marked increase
Grade 2A 
Lamina propria eosinophils
2A.0   No increase
2A.1   Mild but unequivocal increase
2A.2   Moderate increase
2A.3   Marked increase
Grade 2B 
Lamina propria neutrophils 
2B.0   None
2B.1   Mild but unequivocal increase
2B.2   Moderate increase
2B.3   Marked increase
Grade 3 
Neutrophils in epithelium
3.0   None
3.1   <5% crypts involved
3.2   <50% crypts involved
3.3   >50% crypts involved
Grade 4
Crypt destruction
4.0   None
4.1   Probable—local excess of neutrophils in part of crypt
4.2   Probable—marked attenuation
4.3   Unequivocal crypt destruction
Grade 5 
Erosion or ulceration
5.0   No erosion, ulceration, or granulation tissue
5.1   Recovering epithelium + adjacent inflammation
5.2   Probable erosion—focally stripped
5.3   Unequivocal erosion
5.4   Ulcer or granulation tissue
Note: For each histological feature assessed, the highest grade in which there is evidence of disease is assigned. For 
example, if <50% crypts involved is checked (that is, Geboes grade 3 is assigned a 2) and Crypt destruction is 
noted as ‘none’ (4.0) and Erosion or ulceration is ‘No erosion, ulceration, or granulation tissue’ (5.0), the 
participant will be assigned a score of 3.2.
Source: Adapted from Geboes et al.24


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10.11. Appendix 11: Patient-Reported Outcome Instruments
Daily Diary for Review
Stool Frequency
Rectal Bleeding
Nocturnal Stool
Bristol Stool Scale
Urgency NRS
Abdominal Pain NRS
Fatigue NRS
PGR-S
Abbreviations: NRS = numeric rating scale; PGR-S = Patient’s Global Rating of Severity.
The following are additional descriptions of PRO instruments used in the patient eDiary or tablet 
device (and/or a web-based collection system) for this study.
Used in the Patient eDiary
Nocturnal Stool: The Nocturnal Stool instrument is a single item asking the participant to record 
the number of stools they had during the night (or day, for shift workers) causing them to waken 
from sleep. Participants will be provided with an electronic diary tool during screening to record 
information daily pertaining to their nocturnal stool count.
Bristol Stool Scale: The Bristol Stool Scale is a single item that provides a pictorial and verbal 
description of stool consistency and form ranging from Type 1 (Hard Lumps) to Type 7 
(Watery/liquid). Participants will be provided with an electronic diary tool during screening to 
record information daily pertaining to their stool.
Urgency NRS: A single item that measures the severity for the urgency (sudden or immediate 
need) to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no 
urgency) to 10 (worst possible urgency). Participants will be provided with an electronic diary 
tool during screening to record information daily pertaining to their severity of urgency.
Abdominal Pain NRS: A single item that measures the “worst abdominal pain in the past 
24 hours” using an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). 
Participants will be provided with an electronic diary tool during screening to record information 
daily pertaining to their worst abdominal pain experience.
Fatigue NRS: The Fatigue NRS is a single item that measures the “worst fatigue (weariness, 
tiredness) in the past 24 hours” using an 11-point NRS ranging from 0 (no fatigue) to 10 (as bad 
as you can imagine). Participants will be provided with an electronic diary tool during screening 
to record information daily pertaining to their worst fatigue experience.
Patient’s Global Rating of Severity (PGR-S): The PGR-S is a 1-item patient-rated 
questionnaire designed to assess the patients’ rating of their disease symptom severity over the 
past 24 hours. Responses are graded on a 6-point scale in which a score of 1 indicates the 


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participant has no symptoms (that is, “none”) and a score of 6 indicates that the participant’s 
symptom(s) are “very severe.” Participants will be provided with an electronic diary tool during 
screening to record information daily pertaining to their disease experience.
Used in the Tablet Device and/or Web-Based Collection System
Patient’s Global Impression of Change (PGI-C): The PGI-C scale is a patient-rated instrument 
designed to assess the patients’ rating of change in their symptom(s). Responses are graded on a 
7-point Likert scale in which a score of 1 indicates that the subject’s symptom(s) is “very much 
better,” a score of 4 indicates that the subject’s symptom has experienced “no change,” and a 
score of 7 indicates that the subject’s symptom(s) is “very much worse.” Participants will record 
their response to the PGI-C electronically as source data at appropriate visits.
Inflammatory Bowel Disease Questionnaire (IBDQ): A 32-item patient-completed 
questionnaire that measures 4 aspects of patients’ lives: symptoms directly related to the primary 
bowel disturbance, systemic symptoms, emotional function, and social function.21-23 Responses 
are graded on a 7-point Likert scale in which 7 denotes “not a problem at all” and 1 denotes “a 
very severe problem.” Scores range from 32 to 224; a higher score indicates a better quality of 
life. Participants will record their responses to the IBDQ electronically as source data at 
appropriate visits.
16-Item Quick Inventory of Depressive Symptomatology–Self Report (QIDS-SR16): See 
Section 8.2.10.2.


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10.12. Appendix 12: Abbreviations
Term
Definition
5-ASA
5-aminosalicylic acid
6-MP
6-mercaptopurine
ADA
anti-drug antibody
AE
adverse event
AESI
adverse event of special interest
AIDS
acquired immune deficiency syndrome
ALC
absolute lymphocyte count
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANC
absolute neutrophil count
ANCOVA
analysis of covariance
ANOVA
analysis of variance
anti-HBc
antibody to hepatitis B core antigen
AST
aspartate aminotransferase
AUC
area under the concentration versus time curve
AZA
azathioprine
BCG
Bacillus Calmette-Guerin
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 participants are aware of the treatment received.
CFR
United States Code of Federal Regulations
CI
confidence interval
CK
creatine kinase
clinical research 
physician
Individual responsible for the medical conduct of the study. Responsibilities of the 
clinical research physician may be performed by a physician, clinical research 
scientist, global safety physician or other medical officer.
CMH
Cochran–Mantel–Haenszel
CMV
cytomegalovirus


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
1 4 5
Ter m
Def i niti o n
c o m plai nt
A c o m plai nt is a n y writte n, electr o nic, or oral c o m m u nicati o n t hat alle ges 
deficie ncies relate d t o t he i de ntit y, q ualit y, p urit y, d ura bilit y, relia bilit y, safet y or 
effecti ve ness, or perf or ma nce of a dr u g or dr u g deli ver y s yste m.
c o m plia nce
A d here nce t o all st u d y -relate d, g o o d cli nical practice ( G C P), a n d a p plica ble 
re g ulat or y re q uire me nts.
C P K
creati ni ne p h os p h o ki nase (see C K)
C R F
case re p ort f or m (see e C R F)
C R S
c yt oki ne release s y n dr o me
C- S S R S
C ol u m bia – S uici de Se verit y Rati n g Scale
C T
c o m p uterize d t o m o gra p h y
C T A
cli nical trial a gree me nt
C X R
c hest x-ra y
D A L M
d y s plasia-ass ociate d lesi o n or mass
D N A
de o x yri b o n ucleic aci d
E B V
E pstei n -Barr vir us
E C G
electr ocar di o gra m
e C O A
electr o nic Cli nical O utc o me Assess me nt
e C R F
electr o nic case re p ort f or m (see C R F)
E D C
electr o nic data ca pt ure s yste m
e Diar y
electr o nic diar y
e G F R
esti mate d gl o mer ular filtrati o n rate
E nr oll
T he act of assi g ni n g a partici pa nt t o a treat me nt. Partici pa nts w h o are e nr olle d i n t he 
st u d y are t h ose w h o ha ve bee n assi g ne d t o a treat me nt.
E nr oll me nt
T he act or ti me p oi nt of ra n d o mizati o n or treat me nt assi g n me nt , or t he c o n diti o n of 
ha ve bee n assi g ne d t o a treat me nt.
E nt e r
Partici pa nts e ntere d i nt o a st u d y are t h ose w h o si g n t he i nf or me d c o nse nt f or m 
directl y or t hr o u g h t heir le gall y acce pta ble re prese ntati ves.
E R B
Et hical Re vie w B oar d (see I R B)
E S
e n d osc o pic s u bsc ore(s)
E T V
earl y ter mi nati o n visit
C CI
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
1 4 6
Ter m
Def i niti o n
F S H
f ollicle-sti m ulati n g h or m o ne
G C P
g o o d cli nical practice
G G T
ga m ma -gl uta m yl tra nsferase
H Bs A g
he patitis B s urface a nti ge n
H B V
he patitis B vir us
H C V
he patitis C vir us
H D V
he patitis D vir us
HI V
h u ma n i m m u n o deficie nc y vir us
I A C
i nter nal assess me nt c o m mittee
I B
I n vesti gat or’s Br oc h ure
I B D
i nfla m mat or y b o wel disease
I B D- U
i nfla m mat or y b o wel disease u nclassifie d
I B D Q
I nfla m mat or y B o wel Disease Q uesti o n naire
I C F
i nf or me d c o nse nt f or m
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n
I E C
i n de pe n de nt et hics c o m mittee (see I R B)
I g A
i m m u n o gl o b uli n A
I G R A
i nterfer o n ga m ma release assa y
I L
i nterle u ki n
I nf or me d c o nse nt
A pr ocess b y w hic h a partici pa nt v ol u ntaril y c o nfir ms his or her willi n g ness t o 
partici pate i n a partic ular st u d y, after ha vi n g bee n i nf or me d of all as pects of t he 
st u d y t hat are rele va nt t o t he partici pa nt’s decisi o n t o partici pate. I nf or me d c o nse nt 
is d oc u me nte d b y mea ns of a writte n, si g ne d a n d date d i nf or me d c o nse nt f or m.
I N R
i nter nati onal n o r malize d rati o
i nteri m a nalysis
A n i nteri m a nal ysis is a n a nal ysis of cli nical st u d y data, se parate d i nt o treat me nt 
gr o u ps, t hat is c o n d ucte d bef ore t he fi nal re p orti n g data base is create d/l oc ke d.
i n vesti gati o nal pr o d uct 
(I P)
A p har mace utical f or m of a n acti ve i n gre die nt or place b o bei n g teste d o r use d as a 
refere nce i n a cli nical trial, i ncl u di n g pr o d ucts alrea d y o n t he mar ket w he n use d or 
asse m ble d (f or m ulate d or pac ka ge d) i n a wa y differe nt fr o m t he a ut h orize d f or m, or 
mar kete d pr o d ucts use d f or a n u na ut h orize d i n dicati o n, or mar kete d pr o d ucts use d 
t o gai n f urt her i nf or mati o n a b o ut t he a ut h orize d f or m.
I P
i n vesti gati o nal pr o d uct
C CI


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147
Term
Definition
IRB
institutional review board (IRB), also called independent ethics committee (IEC) or 
ethical review board (ERB)
ISR
injection site reaction
IT
information technology
ITT
intent to treat
IV
intravenous
IWRS
interactive web-response system
JAK
Janus kinase
LS
least squares
LTBI
latent tuberculosis infection
MedDRA
Medical Dictionary for Regulatory Activities
mBOCF
modified baseline observation carried forward
MI
multiple imputations
mITT
modified intent-to-treat
MDRD
Modification of Diet in Renal Disease
MMRM
mixed-effects model of repeated measures
MMS
modified Mayo score
NK
natural killer
NONMEM
nonlinear mixed effects modeling
NRI
nonresponder imputation
NRS
numeric rating scale
Participant
Equivalent to Clinical Data Interchange Standards Consortium (CDISC) term 
“subject,” meaning an individual who participates in a clinical trial, either as 
recipient of an investigational medicinal product or as a control.
In this protocol, the term “participant” is used to indicate an individual who 
participates in a clinical trial, either as a recipient of an investigational medicinal 
product or as a control. This usage reflects preferences indicated by patient 
advocates to more accurately reflect the role of people who take part in clinical 
trials. The terms “patient” and “subject” are also used.
PD
Pharmacodynamic
PEG
polyethylene glycol
PGA
Physician’s Global Assessment
PGI-C
Patient’s Global Impression of Change


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Term
Definition
PGR-S
Patient’s Global Rating of Severity
PK
Pharmacokinetic
PK/PD
pharmacokinetics/pharmacodynamics
PPD
purified protein derivative
PRO
patient-reported outcomes
PT-INR
prothrombin time
Q2W
every 2 weeks
QIDS-SR16
16-Item Quick Inventory of Depressive Symptomatology–Self Report
QTc
corrected QT interval
RB
rectal bleeding
RNA
ribonucleic acid
SAE
serious adverse event
SAP
statistical analysis plan
SC
subcutaneous
screen
The act of determining if an individual meets minimum requirements to become 
part of a pool of potential candidates for participation in a clinical study.
SF
stool frequency
SLE
systemic lupus erythematosus
SoA
Schedule of Activities, as described in Section 1.3 of the protocol
SOC
system organ class
study drug
See “study intervention”
study intervention
Any investigational intervention, marketed product, placebo, or medical device 
intended to be administered to a study participant according to the study protocol
subject
see “participant”
TB
tuberculosis
TBL
total bilirubin level
Tcons
conventional T cells
TE-ADA
treatment-emergent anti-drug antibody
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.


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
1 4 9
Ter m
Def i niti o n
T N F
t u m or necr osis fact or
Tre gs
re g ulat or y T cells
T S T
t u berc uli n s ki n test
U C
ulcerati ve c olitis
U L N
u p per li mit of n or mal
W B C
w h ite bl o o d cell c o u nt
W H O
W orl d Healt h Or ga nizati o n
W O C B P
w o me n of c hil d beari n g p ote ntial
C CI


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10.13. Appendix 13: 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
In an exceptional circumstance, after receiving the sponsor’s written approval, sites may
implement changes if permitted by local regulations.
Ethical Review Boards (ERBs), regulatory bodies and any other relevant local authorities, as 
required, will be notified as early as possible to communicate implementation of changes in 
study conduct due to exceptional circumstances. To protect the safety of study participants, 
urgent changes may be implemented before such communications are made, but all changes will 
be reported as soon as possible following implementation. If approval of ERBs, regulatory 
bodies, or both is required per local regulations, confirmation of this approval will be retained in 
the study records.
In the event written approval is granted by the sponsor for changes in study conduct, additional
written guidance, if needed, will be provided by the sponsor.
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

Good Clinical Practice compliance, and

minimization of risk to study integrity.
Such changes are intended to

mitigate risks of participants missing visits

allow participants to continue safely in the study, and

maintain the data integrity of the study.
Informed Consent
Additional consent from the participant will be obtained, as applicable, for


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
participation in remote visits (as defined in the “Changes in Study Conduct” section 
below)

a change in the method, location, or both, of study intervention administration,

dispensation of additional study drug during an extended treatment period

alternate delivery of study intervention and ancillary supplies, and,

provision of their personal or medical information required prior to implementation of 
these activities.
Changes in Study Conduct
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. Missing data 
will be captured as protocol deviations.
1. Remote visits and adjustments to visit interval tolerance
Whenever possible and safe to do so, as determined by the investigator’s discretion, 
participants should complete the usual SoA. To maximize the possibility that the study visits 
can be conducted as on-site visits, the visit interval tolerances (visit windows) may be 
adjusted within the ranges specified in the following table. This minimizes missing data and 
preserves the intended conduct of the study.
The table also shows the acceptable location types for various study visits. Remote options
described in the sponsor’s guidance and written approval may include: a) telephone, 
IT-assisted virtual, or both; b) mobile healthcare; and c) other. More information on these 
options follows the table.
Screening and Induction Period (SOA Table 1)
For this visit...
Permitted Visit Types
Visit Interval Tolerancea
Visit 1
on-site only
same as shown in SOA, but flexibility can be 
considered following consultation with, and with 
prior approval by, the sponsor
Visit 2
on-site only
same as shown in the SOA
Visit 3 through Visit 8
remote
same as shown in the SOA
Visit 9
remote
for endoscopy: 3 days before to 28 days after the 
targeted visit date (inclusive)
for other procedures: same as shown in the SOA
Maintenance Treatment Period (SOA Table 2)
Visit 10 through Visit 28
remote
same as shown in the SOA
Visit 29
remote
for endoscopy: from 3 days before to 56 days after 
the targeted visit date (inclusive)
for other procedures: same as shown in the SOA
Extension Induction and Extension Maintenance Treatment Periods (SOA Table 3)
Visit 10 through Visit 15
remote
same as shown in the SOA


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
1 5 2
Visit 1 6
re m ote
f or e n d osc o p y: fr o m 3 da ys bef ore t o 2 8 da ys after 
t he tar gete d visit date (i ncl usi ve)
f or ot her pr oce d ures: sa me as s h o w n i n t he S O A
Visit 1 7 t hr o u g h Visit 2 8
re m ote
sa me as s h o w n i n t he S O A
Visit 2 9
re m ote
f or e n d osc o p y: fr om 3 da y s bef ore t o 5 6 da ys after 
t he tar gete d visit date (i ncl usi ve)
f or ot her pr oce d ures: sa me as s h o w n i n t he S O A
E arl y ter mi n ati o n, U nsc he d ule d visits, a n d P ost -Tre at me nt F oll o w -U p Peri o d ( S O A T a ble 4)
Earl y  ter mi nati o n visit 
( E T V)
re m ote
f or e n d osc o p y: wit hi n 5 6 da ys after t he earl y 
ter mi nati o n decisi o n
N ote : E n d osc o p y a n d c ol o n bi o ps y sa m ple c ollecti o n
are rec o m me n de d at E T V base d o n j u d g me nt of 
t he i n vesti gat or a n d after disc ussi o n wit h t he 
s p o ns or’s me dical m o nit or. If n ot perf or me d at 
E T V, t his will n ot be c o nsi dere d a pr ot oc ol 
de viati o n. .
f or ot her pr oce d ures: sa me as s h o w n i n t he S O A
Visit 9 9 7
re m ote
n ot a p plica ble
Visit 8 0 1
re m ote
sa me as s h o w n i n t he S O A
Visit 8 0 2
re m ote
sa me as s h o w n i n t he S O A
a N ote: F or partici pa nts w h ose visits ha ve e xte n de d wi n d o ws, a d diti o nal st u d y dr u g ma y  nee d t o be pr o vi de d t o 
a v oi d st u d y dr u g i nterr u pti o n a n d mai ntai n o verall i nte grit y of t he st u d y.
Tele p h o ne, I T-assiste d virt u al visits , or b ot h (tele me dici ne): Tele p h o ne or I T-assiste d
virt ual visit s t o c o mplete a p pr o pri ate assess me nts are acce p ta ble. I n s o urce d oc u me nts, 
t he st u d y sit e s h o uld ca pt ure t he visit l ocati o n a n d met h o d, wit h a s pecific e x pla nat i on f or 
a n y data missi n g beca use of misse d i n-pers o n si te visits. Assess me nts t o be c o m plete d i n 
t his ma n ner ma y i ncl u de, b ut are n ot li mite d to, t o bacc o use assess me nt, e val uat i on of 
 a n d P R Os via a ta blet a n d/ or a we b -base d c ollect i on s yste m .
M o bile he alt hc are:
Heal t hcare visits m a y be perf or me d b y a m o bile heal t hcare pr o vider 
at lo c ati o ns ot her t ha n t he st u d y  site w he n partici pa nts ca n n ot tra vel t o t he site d ue t o a n 
e xce pti o nal circ u msta nce. if writte n a p pr o val is pr o vi de d b y t he s p o ns or. Pr oce d ures 
perf or m e d at s uc h visits ma y i ncl u de, b ut are n ot li mite d t o, vit al si g ns, weig ht, p h ysical 
e xa mi nat i ons , e val uat i ons f or 
 E C Gs , c o llecti on of bl o o d a n d uri ne sa m ples, P R Os 
via a ta blet or a we b -base d c o llecti on s yste m , a n d a d mi nistrati o n of st u d y int er ve nt i on.
Ot her alter n ati ve l oc ati o ns : Pr oce d ures w hic h c o uld be d o ne at a n alter nate l ocat i on i n 
ver y  e xce pt i onal circ u msta nces i ncl u de, b ut are n ot li mite d t o, E C Gs, c hest x -r a ys,
e n d osc o p ies, col o n bi o ps y sa m ple c ollect i ons, c ollecti o ns of bl o o d a n d uri ne sa m ple s.
Re gar dless of t he t y p e of  r e mote visi ts i m ple me nte d, t he pr ot oc ol re q uire me nts re gar di n g t he 
re p orti n g of A Es, S A Es, a n d pr o d uct c o m plai nts re mai n u nc ha n ge d. F urt her m or e, e ver y 
eff ort s h o ul d be ma de t o e na ble partici pa nts t o ret ur n t o o n -site visits as s o on as reas o na bl y 
p ossi ble, w hile e ns uri n g t he safet y of  bot h  t he partici pa nts a n d t he site staff.
2.
L oc al l a b or at or y testi n g o pti o n
L ocal  la b orat or y testi n g ma y be c o n d ucte d i n lie u of ce ntral la b orat or y testi n g. H o we ver, 
ce ntral la b orat or y testi n g must be retai ne d f or t he f oll o wi n g sa m ples:
 P K , 
C CI
C CI
C CI


C O N FI D E N TI A L
Pr ot oc ol  J 1 P-M C -K F A H( b)
1 5 3
 fl ow c y t o metr y pa nel, g e net ics sa m ple, tests of 
 
, a n d tests o btai ne d beca use of a s yste mic 
h y perse nsit i vity e ve nt . T he l ocal la b orat or y m ust be q ualifie d i n acc or da nce wit h a p plica ble 
l ocal re g ulatio ns.
3.
I n vesti g ati o n al pr o d uct a n d a ncill ar y s u p plies (i ncl u di n g p artici p a nt di aries)
W he n a partici pa nt is u na ble t o g o t o t he site t o recei ve st u d y  s u p plies d uri n g n or mal o n-sit e 
visit s, t he site s h o uld w or k wi t h t he s p o ns or t o deter mi ne a p pr o priate acti o ns. T hese acti ons 
ma y i ncl u de

as ki n g t he partici pa nt t o g o t o t he site a n d recei ve st u d y s u p plies fr o m site staff 
wi t ho ut c o m plet i on of a f ull st u d y  visit

as ki n g t he partici pa nt’s desi g nee t o g o t o t he site a n d recei ve st u d y s u p plies o n a 
parti ci pa nt’s be half,

arra n gi n g deli ver y of st u d y s u p plies, a n d

w or ki n g wit h t he s p o ns or t o deter mi ne h o w st u d y  int er ve nt i on is t o be a d mi nistere d 
t o t he partici pa nt, f or e xa m ple, a d mi nistrati o n of  st u d y dr u g t o t he partici pa nt d uri n g 
a mo bile healt hcare visit or at a n alter nate l ocat i on.
T hese re q uire me nts m ust be met bef ore acti o n is ta ke n:

Alt er nate deli ver y of I P s h o uld be perf or me d i n a ma n ner t hat d oes n ot c o m pr o mise 
treat me nt bli n di n g a n d e ns ures pr o d uct i nte grit y.  T he e xisti n g pr ot oc ol re q uire me nts 
f or pr o d uct acc o u nta bility re mai n u nc ha n ge d, i ncl u di n g verificat i on of partici pa nt’s 
receipt of  st u d y s u p plies.

W he n deli veri n g s u p plies t o a l ocat i on ot her t ha n t he st u d y  sit e (for e xa m ple, 
parti ci pa nt’s h o me ), i n vestigat or, s p o ns or, or b ot h s h o ul d e ns ure o versi g ht of t he 
s hi p pi n g pr ocess t o e ns ure acc o u nta bilit y a n d pr o d uct q ualit y (t hat is, st ora ge 
c o n ditio ns mai ntai ne d a n d i ntact pac ka gi n g u p o n recei pt).

I nstr uctio ns ma y  be pr o vi de d t o t he partici pa nt or desi g nee o n t he fi nal dis p ositi on of 
a n y use d or u n use d st u d y s u p plies.
I n a d diti on, if st u d y  int er ve ntio n is t o be a d mi nistere d t o t he partici pa nt d uri n g a m o bile 
healt hcare visit or at a n alter nate l ocati o n, t his a d ditio nal  re q uire me nt must be m et: o nl y  
pers o n nel a ut h orize d b y t he pri mar y  in vesti gat or or b y  t he s p o ns or ma y s u p pl y or a d mi nister 
st u d y int er ve ntio n .
Missi n g E n d osc o pies
D uri n g e xce pti o nal circ u msta nces, s o me sites mi g ht n ot be a ble t o c o n d uct e n d osc o pies. 
G astr oi ntesti nal s ociet ies ha ve rec om me n d e d t hat pati e nts wi t h I B D w h o d o n ot ha ve C O VI D - 1 9 
s h o uld st a y o n I B D t hera pies wit h a g oal of s ustai ni n g re missi on. 3 3, 3 4 F or partici pa nts i n a 
cli nical st u d y, r e mai ni n g o n a n assi g ne d st u d y tr e at me nt mi g ht be pr otect i ve a gai nst i m me diate 
ris k of  disease w orse ni n g or rec urre nce. Re mai ni n g o n st u d y tr e at me nt mi g ht als o alle viate stress 
C CI
C CI


CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
154
for the participant, the healthcare provider, and the medical system insofar as stress is created by 
withdrawing participants study treatment and then needing to find alternative therapies for the 
withdrawn participants.
This section of this appendix addresses the retention of participants in the study who, in the 
opinion of the investigator, could benefit from continuing to receive study treatment, despite 
their inability to have certain protocol-specified endoscopies. Such participants are referred to 
herein as “Impacted Patients.”
A determination of clinical response status, as described in Section 8.1 of the protocol, relies
upon stool frequency and rectal bleeding data. Therefore, if a participant is found to be 
noncompliant with their daily diary entry to the extent that an assessment of clinical response 
status cannot be made, the participant will not be eligible to be regarded as an Impacted Patient.
The investigator or designee must notify the sponsor and make a request to classify a participant 
as an “Impacted Patient.” However, before doing so, the options for extended visit interval 
tolerances (wider windows) should be exhausted. Also, other options to enable performing the 
endoscopy within the allowed timing should be considered, for example, use of an alternate, 
approved endoscopy site. If, after considering these options, an endoscopy must nevertheless be 
missed, the investigator or designee must describe in the Impacted Patient’s source documents
both the reason for the missed endoscopy and the options which were considered but rejected. 
Without data from postbaseline endoscopies, it is not possible to use per protocol criteria to 
determine the participant’s status as a responder or nonresponder at the end of the Induction 
Period or to determine a participant’s response to Extension Induction or Extension Maintenance
dosing, or to determine clinical response/remission status at Week 52.
Therefore, when Impacted Patients miss any of the endoscopies after randomization, then, 
instead of the protocol-defined clinical response definition, a standardized Clinical Benefit 
criterion will be used for Impacted Patients.
The specific definition of Clinical Benefit for Impacted Patients will be provided separately from 
the protocol.
Impacted Patients who demonstrate Clinical Benefit at Week 12 will enter the blinded 
maintenance period. Impacted Patients who do not demonstrate Clinical Benefit at Week 12 will 
enter the extension induction period.
Impacted Patients who demonstrate Clinical Benefit at the end of the extension induction period 
will enter the extension maintenance period, whereas those who do not will undergo early 
discontinuation procedures.
Documentation
Documentation of changes in study content
Changes to study conduct will be documented.


CONFIDENTIAL
Protocol J1P-MC-KFAH(b)
155
Sites will identify and document the details of how participants, visits 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 generated at a location other than the study site should be part of the 
investigator’s source documentation and should be transferred to the site in a secure and timely 
manner.
Missing data and other protocol deviations
Missing data will be captured as protocol deviations. The study site should document specific 
explanations for any missing data and other protocol deviations. Although protocol deviations 
may be unavoidable in an exceptional circumstance, documentation of protocol deviations and 
missing data will be important for data analysis and reporting.


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Protocol J1P-MC-KFAH(b)
156
11. References
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L e o  D o c u m e n t  I D  =  2 d 0 3 8 f 0 9 - b b b 0 - 4 1 8 a - 9 e 5 7 - d e 2 c 5 b 4 5 6 f e b
A p p r o v e r :  
A p p r o v a l  D a t e  &  T i m e :  0 3 - J u n - 2 0 2 1  1 6 : 2 6 : 0 1  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
A p p r o v e r :  
A p p r o v a l  D a t e  &  T i m e :  0 3 - J u n - 2 0 2 1  1 6 : 4 4 : 3 0  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
P P D
P P D

SAP_001.pdf: 
 
 
 
 
 J1P-MC-KFAH StaƟsƟcal Analysis Plan Version 1 
 
An AdapƟve Phase 2, Randomized, Double-Blind, Placebo-
Controlled Study of LY3471851 (NKTR-358) in PaƟents with 
Moderately to Severely AcƟve UlceraƟve ColiƟs 
 
NCT04677179 
 
Approval Date: 18 Mar 2022 


CONFIDENTIAL 
J1P-MC-KFAH Statistical Analysis Plan Version 1 
LY3471851 
PAGE 1 
Protocol Title: An Adaptive Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of 
LY3471851 (NKTR-358) in Patients with Moderately to Severely Active Ulcerative Colitis 
Protocol Number: J1P-MC-KFAH 
Compound Number: LY3471851 
Short Title: INSTRUCT-UC 
Sponsor Name: Eli Lilly and Company 
Legal Registered Address: Indianapolis, Indiana USA 46285 
Regulatory Agency Identifier Number(s) 
Registry 
ID 
IND 
EudraCT 
151216 
2020-003017-35 
 
 
Confidential Information  
The information contained in this document is confidential and the information contained 
within it may not be reproduced or otherwise disseminated without the approval of Eli Lilly 
and Company or its subsidiaries 
Note to Regulatory Authorities:  This document may contain protected personal data 
and/or commercially confidential information exempt from public disclosure. Eli Lilly and 
Company requests consultation regarding release/redaction prior to any public release. In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.  
 
 
 
 
Approved on 18 Mar 2022 GMT


CONFIDENTIAL 
J1P-MC-KFAH Statistical Analysis Plan Version 1 
LY3471851 
PAGE 2 
Table of Contents 
Table of Contents ...........................................................................................................................2 
Version history ...............................................................................................................................4 
1. 
Introduction .....................................................................................................................5 
1.1. 
Objectives, Endpoints, and Estimands ..............................................................................6 
1.2. 
Study Design ...................................................................................................................12 
1.2.1. 
Method of Assignment to Treatment ..............................................................................15 
2. 
Statistical Hypotheses ...................................................................................................16 
2.1. 
Multiplicity Adjustment ..................................................................................................16 
3. 
Analysis Sets ..................................................................................................................17 
4. 
Statistical Analyses .......................................................................................................18 
4.1. 
General Considerations ...................................................................................................18 
4.1.1. 
Analysis Methods............................................................................................................18 
4.1.2. 
Handling of Dropouts or Missing Data ...........................................................................20 
4.2. 
Participant Dispositions ..................................................................................................21 
4.3. 
Primary Endpoint Analysis .............................................................................................21 
4.3.1. 
Definition of endpoint .....................................................................................................21 
4.3.2. 
Main analytical approach ................................................................................................21 
4.3.3. 
Bayesian Model Averaging.............................................................................................22 
4.4. 
Secondary Endpoints Analyses .......................................................................................23 
4.4.1. 
Secondary Efficacy Endpoints ........................................................................................23 
4.4.2. 
Secondary Health Outcome Endpoints ...........................................................................24 
4.4.3. 
Bioanalytical and Pharmacokinetic/Pharmacodynamic Methods ...................................25 
4.5. 
Tertiary/Exploratory Endpoints Analyses ......................................................................25 
4.5.1. 
Exploratory Efficacy Analysis ........................................................................................25 
4.6. 
Safety Analyses...............................................................................................................26 
4.6.1. 
Extent of Exposure ..........................................................................................................27 
4.6.2. 
Adverse Events ...............................................................................................................28 
4.6.3. 
Adverse Events of Special Interest .................................................................................30 
4.6.4. 
Injection Site Reaction ....................................................................................................33 
4.6.5. 
Clinical Laboratory Evaluation .......................................................................................34 
4.6.6. 
Vital Signs and Other Physical Characteristics ..............................................................37 
4.6.7. 
Electrocardiograms .........................................................................................................38 
4.6.8. 
38 
4.7. 
Other Analyses ................................................................................................................40 
4.7.1. 
Efficacy Subgroup Analysis ...........................................................................................40 
4.7.2. 
Safety Subgroup Analyses ..............................................................................................41 
4.8. 
Interim Analyses .............................................................................................................41 
4.8.1. 
Data Monitoring Committee (DMC) ..............................................................................42 
4.9. 
Changes to Protocol-Planned Analyses ..........................................................................42 
5. 
Sample Size Determination ..........................................................................................43 
6. 
Supporting Documentation ..........................................................................................44 
6.1. 
Appendix 1: Demographic and Baseline Characteristics ...............................................44 
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6.2. 
Appendix 2: Treatment Compliance ...............................................................................44 
6.3. 
Appendix 3: Clinical Trial Registry Analyses ................................................................45 
6.4. 
Appendix 4: Daily Diary Calculations............................................................................45 
6.5. 
Appendix 5: List of MedDRA Preferred Terms for Potential 
Opportunistic Infections (POI) .......................................................................................48 
6.6. 
Appendix 6: List of MedDRA Preferred Terms for Elevated or 
Increased Lipids from the Dyslipidemia SMQ (SMQ20000026) ...................................63 
6.7. 
Appendix 7: List of Planned Laboratory Analytes with Reference 
Range Sources.................................................................................................................64 
7. 
References ......................................................................................................................68 
 
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Version history 
This Statistical Analysis Plan (SAP) for study J1P-MC-KFAH (KFAH) is based on the protocol 
dated 18Nov2020 and approved prior to unblinding. 
Table KFAH.1. 
SAP Version History Summary 
SAP 
Version 
Approval 
Date 
Change 
Rationale 
1 
 
Not Applicable 
Original version 
 
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1. 
Introduction 
Study J1P-MC-KFAH is an adaptive Phase 2, randomized, double-blind, placebo-controlled trial 
of LY3471851 (NKTR-358) in patients with moderately to severely active ulcerative colitis. 
There are no changes to the analyses described in the protocol. 
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1.1. 
Objectives, Endpoints, and Estimands 
 
Objectives 
Endpoints 
Primary 
 
 To determine whether LY3471851 is 
superior to placebo in inducing clinical 
remission at Week 12 in patients with 
moderately to severely active ulcerative 
colitis (UC) 
 The difference in the proportion of 
participants who achieve clinical 
remission based on MMS at Week 12 
without permanently discontinuing 
treatment  
Secondary 
 
 To evaluate the efficacy of induction 
treatment with LY3471851 compared 
to placebo with respect to clinical, 
endoscopic, and histologic 
improvement 
 The difference between LY3471851 
and placebo in the proportion of 
participants who have not permanently 
discontinued at Week 12 and have 
achieved at Week 12: 
o clinical response 
o endoscopic remission 
o endoscopic response 
o symptomatic remission 
o symptomatic response 
o histologic remission 
o histologic-endoscopic mucosal 
healing 
 To evaluate the efficacy of maintenance 
treatment with LY3471851 compared 
to placebo with respect to clinical, 
 The difference between LY3471851 
and placebo in the proportion of 
participants who were responders at 
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endoscopic, and histologic 
improvement 
Week 12 (Week 12 Responders) and 
have not permanently discontinued at 
Week 52, who at Week 52 still have: 
o clinical remission 
o clinical response 
o endoscopic remission 
o endoscopic response 
o symptomatic remission 
o symptomatic response 
o histologic remission 
o histologic-endoscopic mucosal 
healing 
 To evaluate the efficacy of treatment 
with LY3471851 compared to placebo 
with respect to patient-reported 
outcomes and quality of life measures 
 Comparison of mean changes from 
baseline to Week 12 and to Week 52 in 
scores for  
o IBDQ 
o Urgency NRS 
o Abdominal Pain NRS 
o Nocturnal Stools 
o Bristol Stool Scale 
o PGR-S 
o Fatigue NRS 
 To evaluate the PK of LY3471851 
 Week 12 LY3471851 trough 
concentrations 
Tertiary/Exploratory 
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Abbreviations: 
; IBDQ = Inflammatory Bowel Disease Questionnaire; MMS = 
modified Mayo score, NRS = numeric rating scale; PGR-S = Patient’s Global Rating of Severity; PK = 
pharmacokinetics; UC = ulcerative colitis; 
. 
Primary estimand 
The primary clinical question of interest is: What is the intervention difference in successful response rate of clinical remission based 
on MMS at Week 12 of intervention in patients with moderately to severely active UC, where successful response is defined as patient 
who achieves clinical remission without discontinuing treatment, without increasing mandatory stable medications, and without taking 
prohibited medications prior to the time point of interest? The primary comparison will be assessed using a composite estimand 
strategy to address the intercurrent events.    
The estimand is described by the following attributes: 
Population: patients with moderately to severely active UC. Further details can be found in Section 3. 
Endpoint: clinical remission based on MMS at Week 12 in MMS. 
Treatment condition: the randomized treatment without rescue medication or change in background medication (treatment policy 
strategy). Further details on study interventions and concomitant, including rescue, interventions can be found in Section 6. 
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The 2 intercurrent events “intervention discontinuation for any reason” and “initiation of rescue intervention or change in background 
intervention” are both addressed by the treatment condition of interest attribute. There are no remaining intercurrent events. 
Population-level summary: difference in proportion of participants achieving clinical remission at Week 12 between intervention 
conditions. 
Rationale for estimand: The data collected after the treatment discontinuation or post-rescue medication will be categorized as 
nonresponder. 
 
Secondary estimands 
1) Clinical response / endoscopic remission / endoscopic response / symptomatic remission / symptomatic response / histologic 
remission / histologic-endoscopic mucosal healing at Week 12 
The secondary clinical question of interest is: What is the intervention difference in successful response rate of clinical response / 
endoscopic remission / endoscopic response / symptomatic remission / symptomatic response / histologic remission / histologic-
endoscopic mucosal healing at Week 12 of intervention in patients with moderately to severely active UC, where successful response 
is defined as patient who achieves clinical response / endoscopic remission / endoscopic response / symptomatic remission / 
symptomatic response / histologic remission / histologic-endoscopic mucosal healing without discontinuing treatment, without 
increasing mandatory stable medications, and without taking prohibited medications prior to the time point of interest? The secondary 
comparisons will be assessed using a composite estimand strategy to address the intercurrent events.    
The estimand is described by the following attributes: 
Population: patients with moderately to severely active UC who have not permanently discontinued at Week 12 and have achieved at 
Week 12. Further details can be found in Section 3. 
Endpoint: clinical response / endoscopic remission / endoscopic response / symptomatic remission / symptomatic response / histologic 
remission / histologic-endoscopic mucosal healing at Week 12. 
Treatment condition: the randomized treatment without rescue medication or change in background medication (treatment policy 
strategy). Further details on study interventions and concomitant, including rescue, interventions can be found in Section 6. 
The 2 intercurrent events “intervention discontinuation for any reason” and “initiation of rescue intervention or change in background 
intervention “ are both addressed by the treatment condition of interest attribute. There are no remaining intercurrent events. 
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Population-level summary: difference in proportion of participants achieving clinical response / endoscopic remission / endoscopic 
response / symptomatic remission / symptomatic response / histologic remission / histologic-endoscopic mucosal healing at Week 12 
between intervention conditions. 
Rationale for estimand: The data collected after the treatment discontinuation or post-rescue medication will be categorized as 
nonresponder. 
2) Clinical remission / clinical response / endoscopic remission / endoscopic response / symptomatic remission / symptomatic 
response / histologic remission / histologic-endoscopic mucosal healing at Week 52 
The secondary clinical question of interest is: What is the intervention difference in successful response rate of clinical response / 
endoscopic remission / endoscopic response / symptomatic remission / symptomatic response / histologic remission / histologic-
endoscopic mucosal healing at Week 52 of intervention in patients with moderately to severely active UC, where successful response 
is defined as patient who achieves clinical response / endoscopic remission / endoscopic response / symptomatic remission / 
symptomatic response / histologic remission / histologic-endoscopic mucosal healing without discontinuing treatment, without 
increasing mandatory stable medications, and without taking prohibited medications prior to the time point of interest? 
The estimand is described by the following attributes: 
Population: patients with moderately to severely active UC who were responders at Week 12, have not permanently discontinued at 
Week 52, have achieved at Week 52. Further details can be found in Section 3. 
Endpoint: clinical remission / clinical response / endoscopic remission / endoscopic response / symptomatic remission / symptomatic 
response / histologic remission / histologic-endoscopic mucosal healing at Week 52. 
Treatment condition: the randomized treatment without rescue medication or change in background medication (treatment policy 
strategy). Further details on study interventions and concomitant, including rescue, interventions can be found in Section 6. 
The 2 intercurrent events “intervention discontinuation for any reason” and “initiation of rescue intervention or change in background 
intervention “ are both addressed by the treatment condition of interest attribute. There are no remaining intercurrent events. 
Population-level summary: difference in percentage of participants achieving clinical remission / clinical response / endoscopic 
remission / endoscopic response / symptomatic remission / symptomatic response / histologic remission / histologic-endoscopic 
mucosal healing at Week 52 between intervention conditions. 
Rationale for estimand: The data collected after the treatment discontinuation or post-rescue medication will be categorized as 
nonresponder. 
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3) IBDQ / Urgency NRS / Abdominal Pain NRS / Nocturnal Stools / Bristol Stool Scale / PGR-S / Fatigue NRS 
The secondary clinical question of interest is: What is the intervention difference in IBDQ / Urgency NRS / Abdominal Pain NRS / 
Nocturnal Stools / Bristol Stool Scale / PGR-S / Fatigue NRS at Week 12 and Week 52 of intervention in patients with moderately to 
severely active UC regardless of intervention discontinuation for any reason and regardless of initiation of rescue intervention or 
change in background intervention? 
The estimand is described by the following attributes: 
Population: patients with moderately to severely active UC. Further details can be found in Section 3. 
Endpoint: IBDQ / Urgency NRS / Abdominal Pain NRS / Nocturnal Stools / Bristol Stool Scale / PGR-S / Fatigue NRS at Week 12 
and Week 52. 
Treatment condition: the randomized treatment without rescue medication or change in background medication (treatment policy 
strategy). Further details on study interventions and concomitant, including rescue, interventions can be found in Section 6. 
The 2 intercurrent events “intervention discontinuation for any reason” and “initiation of rescue intervention or change in background 
intervention “ are both addressed by the treatment condition of interest attribute. There are no remaining intercurrent events. 
Population-level summary: difference in mean change in IBDQ / Urgency NRS / Abdominal Pain NRS / Nocturnal Stools / Bristol 
Stool Scale / PGR-S / Fatigue NRS at Week 12 and Week 52 between intervention conditions. 
Rationale for estimand: The data collected after the treatment discontinuation or post-rescue medication will not represent the true 
efficacy effects. 
 
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1.2. 
Study Design 
Study KFAH is an adaptive Phase 2 multicenter, randomized, double-blind, placebo-controlled, 
parallel-group study to evaluate the efficacy and safety of multiple dose levels of LY3471851 in 
adult patients with moderately to severely active UC. Enrolled study participants will have either  
 an inadequate response to, loss of response to, or be intolerant to corticosteroid or 
immunomodulator therapy for UC (termed “conventional-failed”), or 
 an inadequate response to, loss of response to, or are intolerant to biologic or JAK 
inhibitor therapy for UC (termed “advanced therapy-failed”). 
Study Stages 
This adaptive study has two stages. 
Stage 1: 
Approximately 100 participants will be randomly assigned to one of three 
treatment groups, including placebo. Interim analyses will be conducted for 
safety, dosing tolerability, and efficacy. These interim analyses will determine the 
doses to be used in Stage 2.  
Note: Participants enrolled during Stage 1 of the study will remain on their 
randomly assigned Stage 1 doses. Their doses will be changed only if necessary 
due to safety reasons or due to their clinical response status at the end of Stage 1. 
Stage 2: 
Approximately 100 additional study participants will be enrolled and randomly 
assigned to study treatment groups as well as placebo. The treatment doses used 
in Stage 2 may include any of the doses used in Stage1, as well as one or more 
additional LY3471851 doses, not exceeding1800 µg. The Stage 2 LY3471851 
treatment doses will be determined by the sponsor based on results of the Stage 1 
interim analyses and recommendations of the sponsor’s IAC. A small group of 
sponsor personnel having pre-identified roles and no contact with investigative 
sites may review the IAC recommendation and may also review unblinded data in 
order to further assess the recommendation. The IAC charter that describes the 
process for internal decision-making and action plan will be provided. 
Thus, whereas Stage 1 will have three treatment groups (including placebo), Stage 2 could have 
more treatment groups or fewer (including placebo). 
The sponsor intends for the transition from Stage 1 to Stage 2 to be seamless, with participant 
screening and enrollment activities occurring continuously in the transition period. The study 
IWRS will allocate newly enrolling participants to groups according to the Stage 1 
randomization ratio until the Stage 2 groups have been decided upon and implemented. 
The randomization ratios are described in Section 1.2.1. 
Study Periods 
This study has multiple periods. 
Screening period 
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This period begins with Visit 1, which occurs 5 weeks (or less) before the planned randomization 
visit. A participant’s screening evaluations must be completed and reviewed to confirm the 
participant’s eligibility before randomization and dosing occurs at Visit 2. 
Blinded induction and blinded maintenance periods 
The double-blind, placebo-controlled, 12-week induction treatment period begins at Visit 2. 
Dosing, sample collection, and assessments continue Q2W, as shown in the SOA in the protocol. 
Between Week 12 and Week 14, based on samples and assessments collected at Week 12, 
participants will be classified as either “Week 12 Responders” or “Week 12 Nonresponders” 
based on the “clinical response” criteria defined in the protocol. 
 “Week 12 Responders” will continue to receive their same randomly assigned treatment 
throughout the blinded 40-week Maintenance Period, with the final dose occurring at 
Week 50 and the last maintenance assessments and sample collections at Week 52. 
 “Week 12 Nonresponders” will enter the Extension Induction and Extension Maintenance 
Periods. 
Extension induction and maintenance periods  
Beginning at Week 14, participants who were classified as Week 12 Nonresponders will receive 
the high dose (
 µg) of LY3471851 Q2W, unless a lower dose is selected for Stage 2 based 
on interim analyses. 
Between Week 26 and Week 28, based on samples and assessments collected at Week 26, these 
participants will again be classified according to their clinical response status based on MMS 
(responder or nonresponder). 
 Participants who are classified as responders based on the samples and assessments at 
Week 26 will continue to receive LY3471851 Q2W as maintenance through the 
remainder of the study. These participants have their final dose at Week 50 and their last 
maintenance assessments and sample collections at Week 52.  
 Participants who are classified as nonresponders based on the Week 26 samples and 
assessments will be permanently discontinued from study drug when his/her status as a 
nonresponder has been determined; such participants will enter the post-treatment 
follow-up period. 
Post-treatment follow-up period 
All participants will have a post-treatment follow-up visit (Visit 801) for safety assessments. 
Visit 801 occurs approximately 6 weeks after the Week 52 visit. The last dose of study drug is 
given at Week 50. Thus, participants will have been withdrawn from study drug for 
approximately 8 weeks at Visit 801. Participants who were positive for anti-HBc at screening 
will have one additional post-treatment follow-up visit (Visit 802). 
Early discontinuation 
Participants who permanently discontinue the study drug early or withdraw from the study will 
undergo early termination procedures, including an ETV and the post-treatment follow-up visits 
specified in the SoA. 
Figure KFAH.1 and Figure KFAH.2 show the study design. 
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Abbreviations: D = day; DNA = deoxyribonucleic acid; ETV = early termination visit; HBV = hepatitis B virus; 
LY= LY3471851; Q2W = every 2 weeks; W = Week; w = weeks. 
Figure KFAH.1. Study Schematic (Induction and Maintenance Periods) 
 
Abbreviations: DNA = deoxyribonucleic acid; ETV = early termination visit; HBV = hepatitis B virus; Q2W = 
every 2 weeks; W = Week; w = weeks.  
Note: The extension dose could be lower than 
 µg LY3471851, based on interim analyses. 
Figure KFAH.2. Study Schematic (Nonresponder Extension Periods) 
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1.2.1. 
Method of Assignment to Treatment 
Patients who meet all criteria for enrollment will be randomized to treatment at the baseline visit. 
Assignment to treatment groups will be determined by a computer-generated random sequence 
using an interactive web-response system (IWRS), and then the site will be responsible for 
administering the treatment to the patients.  
During Induction Period in Stage 1, approximately 100 participants will be randomized to 1 of 3 
treatment groups in a 2:2:1 ratio: 
 
 µg LY3471851 Q2W SC, 
 
 µg LY3471851 Q2W SC, or 
 placebo. 
During Induction Period in Stage 2, up to approximately 100 additional participants will be 
randomized. The number of treatment groups and randomization ratio for Stage 2 will be 
determined and documented based on the last interim analysis of Stage 1. This decision making 
will occur following Stage 1, and the choice in allocation ratio including placebo may be 
adjusted to achieve the planned allocation across treatment arms. 
The randomization will be stratified based on the following factors: 
 previous advanced therapy failure status (yes/no) 
 baseline corticosteroid use (yes/no), and 
 baseline disease activity (MMS: [4 to 6] or [7 to 9]). 
After the Induction Period, participants enter either Maintenance Period or Extension Induction 
and Extension Maintenance Periods, based on samples and assessments collected at Week 12, as 
described in Section 1.2. 
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2. 
Statistical Hypotheses 
The primary objective is to demonstrate that LY3471851 is superior to placebo in achieving 
clinical remission at Week 12. Thus, the null hypothesis to be tested in relation to the primary 
estimand is that LY3471851 is not different from placebo with respect to the achievement of 
clinical remission at Week 12. 
2.1. 
Multiplicity Adjustment 
Multiplicity adjustment will not be employed in the analysis for this study. 
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3. 
Analysis Sets 
Table KFAH.2 describes the populations planned for use in the analyses. The mITT population, 
as defined below, will be used in analyses of efficacy and PRO, unless otherwise noted in the 
SAP. 
Table KFAH.2. 
Analysis Populations 
Population 
Description 
ITT Population 
All randomized participants. Participants will be analyzed 
according to the treatment to which they were assigned. 
mITT Population 
All randomized participants who receive at least 1 dose of 
study treatment (regardless of whether the participant fails to 
receive the correct treatment, or otherwise fails to follow the 
protocol). Participants will be analyzed according to the 
treatment to which they were assigned. 
Safety Population 
Same as mITT population 
Pharmacokinetic Evaluable 
All participants who receive at least 1 dose of investigational 
product and have sufficient blood sampling to allow for 
pharmacokinetic evaluation. 
Abbreviations: GCP = Good Clinical Practice; ITT = intent-to-treat; mITT = modified intent-to-treat; SAP = 
statistical analysis plan. 
Analyses of the maintenance dosing period and the extension periods will be based on the 
corresponding enrolled population as described in the table above. 
 
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4. 
Statistical Analyses 
4.1. 
General Considerations 
This SAP is intended to describe the analyses of all objectives, as well as safety assessments, for 
study KFAH.   
Statistical analysis of this study will be the responsibility of Eli Lilly and Company (hereafter 
Lilly) or its designee. For primary and key secondary objectives, statistical analyses will be 
performed using SAS® Enterprise 7.1 or higher, SAS® Version 9.4 or higher, or RStudio Server 
Pro Version R.3.6.3. or higher.   
Efficacy analyses will be conducted on the mITT population. Safety analyses will be conducted 
on the Safety population (same as mITT population, as described in Section 3). The efficacy 
analysis of the primary endpoint and secondary endpoints will be repeated for ITT population. 
Additional safety analyses may be performed as deemed appropriate. 
The baseline modified Mayo Score (MMS) is calculated from valid daily diary entries obtained 
prior to endoscopy during the screening period and the endoscopic appearance of the mucosa at 
this screening endoscopy. For other efficacy, health outcome and safety assessments, baseline is 
defined as the last non-missing assessment recorded on or prior to the date of the randomization 
visit (Visit 2). 
Any change to the data analysis 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 clinical study report. Additional exploratory analyses of the data will be conducted as 
deemed appropriate. 
Not all displays and analyses described in this SAP will necessarily be included in the CSR.  Not 
all displays will necessarily be created as a “static” display.  Some displays may be incorporated 
as interactive display tools instead of or in addition to a static display.  Any display described in 
this SAP and not provided in CSR would be available upon request. 
4.1.1. 
Analysis Methods 
Continuous data will be summarized in terms of the number of observations, mean, standard 
deviation (SD), median, minimum, and maximum. The minimum and maximum will be reported 
to the same number of decimal places as the raw data recorded in the database. The mean and 
median will be reported to one more decimal place than the raw data recorded in the database. 
The SD will be reported to two more decimal places than the raw data recorded in the database. 
In general, the maximum number of decimal places reported shall be four for any summary 
statistic. 
Categorical data will be summarized in terms of the number of patients providing data at the 
relevant time point (n), frequency counts and percentages. Percentages will be presented to one 
decimal place. Percentages will be calculated using n (the number of observations with non-
missing values) as the denominator. 
Unless otherwise specified, analysis of hypotheses will be tested without multiplicity control at a 
significance level of 0.05. A 2-sided 95% CI will be provided along with the p-value. P-values 
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which are greater than or equal to 0.001, and less than or equal to 0.999, will be presented to 
three decimal places. All other p-values which are less than 0.001 will be presented as ‘<0.001’, 
while p-values greater than 0.999 will be presented as ‘>0.999’. CIs will be presented to one 
more decimal place than the raw data. 
Unless otherwise specified, variables will be analyzed in the original scale on which they are 
measured. However, if it is deemed more statistically appropriate, a transformation, such as to 
the logarithmic scale, may be applied before analysis. The parametric approach will be employed 
by default for statistical analysis except when nonparametric analysis, such as by a rank-based 
method, is considered to be more fitting.  
For assessments of the primary endpoint, other categorical (binary) efficacy, the Cochran-
Mantel-Haenszel (CMH) chi-square test will be used to compare the treatment groups with the 
following factors:  
 previous advanced therapy failure status (yes/no) 
 baseline corticosteroid use (yes/no) 
 baseline disease activity (MMS: [4 to 6] or [7 to 9]), and 
 region (North America/Europe/Other). 
The CMH chi-square p-value and the relative risk along with its 2-sided CI will be provided. In 
addition, the absolute treatment difference in proportions will be provided along with the 2-sided 
CI estimate. The differences between each treatment group and placebo will also be tested 
separately using a logistic regression model that controls for at least previous advanced therapy 
failure status (yes/no) and corticosteroid use (yes/no). If deemed necessary, additional analyses 
of categorical efficacy variables may be conducted to address sparse data and/or small sample 
sizes. 
Treatment comparisons of continuous efficacy and health outcome variables with multiple 
postbaseline time points will be made using MMRM analysis. The MMRM will include the 
following effects and covariates: 
 treatment group 
 previous advanced therapy failure status (yes/no) 
 corticosteroid use (yes/no) 
 disease activity (MMS: [4 to 6] or [7 to 9]) at baseline) 
 region (North America/Europe/Other) 
 baseline value in the model 
 visit, and  
 the interactions of treatment-by-visit and baseline-by-visit as fixed factors. 
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 heterogeneous autoregressive covariance structure, will be 
used. The first structure to yield convergence will be used for inference. The Newton-Raphson 
with ridging optimization technique will be used to aid with convergence. The Kenward-Roger 
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method 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. 
Treatment group comparisons with placebo at Week 12 and all other appropriate time points will 
be tested. 
Treatment comparisons of continuous efficacy and health outcome variables with a single 
postbaseline time point will be made using ANCOVA with the following in the model:   
 treatment group 
 previous advanced therapy failure status (yes/no) 
 corticosteroid use (yes/no) 
 disease activity (MMS: [4 to 6] or [7 to 9]) at baseline) 
 region (North America/Europe/Other), and 
 baseline value. 
Type III sums of squares for LS means will be used for statistical comparison between treatment 
groups. The LS mean difference, standard error, p-value, and 95% CI, unless otherwise 
specified, will also be reported.  
4.1.2. 
Handling of Dropouts or Missing Data 
Intercurrent events (FDA 2017) are events which occur after the study intervention initiation and 
make it impossible to measure a variable or influence how it should be interpreted. Examples of 
such events include treatment discontinuation due to death or adverse events (AEs), rescue 
treatment, and loss to follow-up.  The missing data handling methods described below describe 
how intercurrent events will be used for the different estimands. 
4.1.2.1. 
Non-Responder Imputation (NRI) 
The primary outcome is the proportion of patients with clinical remission at Week 12. For this 
and other categorical efficacy endpoints (for example, clinical remission (week 52), clinical 
response (week 12, 52), and endoscopic remission (week 12, 52)), non-responder imputation 
(NRI) will be used for missing clinical assessment values. Specifically, all patients who 
discontinue from the study at any time prior to week 12 for any reason or fail to have an 
adequate week 12 efficacy assessment will be considered a non-responder at week 12. Patients 
who discontinue from the study for any reason at any time prior to week 52 after having enrolled 
into the Maintenance Period or fail to have an adequate week 52 efficacy assessment, will be 
considered a non-responder at week 52. 
The NRI may be applied at any time point specified for analysis. 
4.1.2.2. 
Mixed-Effects Model for Repeated Measures 
For the continuous secondary and exploratory efficacy and health outcome variables, MMRM 
analyses will be the main method to mitigate the impact of missing data.  This approach assumes 
that missing observations are missing-at-random (missingness is related to observed data) during 
the study and takes into account both the missingness of data and the correlation of the repeated 
measurements. 
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All continuous endpoints will utilize MMRM to patients who permanently discontinued study 
drug or who were rescued.     
4.1.2.3. 
Modified Baseline Observations Carried Forward (mBOCF) 
For patients discontinuing investigational product due to an AE, the baseline observation for the 
endpoint will be carried forward to the corresponding visit for all missing observations after the 
patient discontinued study treatment.  For patients discontinuing investigational product for any 
other reason, the last non-missing postbaseline observation before discontinuation will be carried 
forward to the corresponding visit for all missing observations after the patient discontinued.  For 
all patients with sporadically missing observations prior to discontinuation, the last non-missing 
observation before the sporadically missing observation will be carried forward to the 
corresponding visit.  Randomized patients without at least 1 postbaseline observation will not be 
included for evaluation with the exception of patients discontinuing study treatment due to an 
AE. 
The mBOCF method is based on an estimand that handles the intercurrent event of discontinuing 
study drug due to an AE by defining the patient as not receiving any benefit from study drug 
after the event.  That is the patient is defined as reverting back to baseline regardless of any 
continuing efficacy benefits they may still have received after the event.  For other intercurrent 
events (e.g., rescue treatment and discontinuation due to reasons other than an AE) or sporadic 
missingness the “while on treatment” strategy is applied.  That is, the endpoint is defined as the 
last observed value at or before the visit of interest before the patient discontinued study 
treatment. 
4.2. 
Participant Dispositions 
A detailed description of participant disposition will be provided, including a summary of the 
number and percentage of participants entered into the study and randomized, the number and 
percentage of participants who complete the study or discontinue, both overall and by reason for 
discontinuation, and the frequency and percentage of patients who discontinue study treatment. 
A summary of important protocol deviations will be provided. 
4.3. 
Primary Endpoint Analysis 
4.3.1. 
Definition of endpoint 
Rate of clinical remission at Week 12 is the primary efficacy outcome for this study and will be 
analyzed using the mITT population. 
Clinical remission is defined as achieving a rectal bleeding (RB) subscore of 0, and stool 
frequency subscore (SF) of 0, or 1 with a decrease of ≥1 point from baseline, and endoscopic 
(ES) subscore of 0 or 1, excluding friability. SF and RB subscores are calculated by averaging 
and rounding the 4-point daily scores over 3 days as described in 6.6.  
4.3.2. 
Main analytical approach 
The primary objective of this study is to test the hypothesis that treatment with LY3471851 is 
superior to placebo in inducing clinical remission at Week 12 in patients with moderate to severe 
ulcerative colitis (UC). 
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The rates of clinical remission and non-remission will be summarized by treatment group and by 
the stratification factors, previous advanced therapy failure status (yes/no), baseline 
corticosteroid use (yes/no), baseline disease activity (MMS: [4 to 6] or [7 to 9]), and region 
(North America/Europe/Other).  
The primary analysis will use the CMH chi-square test to compare LY3471851 to placebo at 
Week 12. The stratification factors used for CMH test are (a) previous advanced therapy failure 
status (yes/no), (b) baseline corticosteroid use (yes/no), (c) baseline disease activity (MMS: [4 to 
6] or [7 to 9]), and (d) region (North America/Europe/Other). See Section 4.1.1 for details on the 
methods to be used to test the differences between each active treatment arm and placebo. 
Ninety five percent confidence interval along with the p-value for the difference in proportions 
(LY arm – placebo) for each pairwise comparison will be obtained. For a pairwise comparison, if 
p-value is less than 0.05, then that LY arm will be considered to be superior to placebo. 
A composite strategy is proposed for other intercurrent events including discontinuing study 
intervention, taking prohibited medications or increase the dose of mandatory stable medications. 
The NRI methodology described in Section 4.1.2.1 will be applied when any of these events 
occur.  
4.3.3. 
Bayesian Model Averaging 
A Bayesian model averaging will be performed for additional analysis of the clinical remission at 
Week 12. A Bayesian model averaging (BMA) approach will be used to estimate the dose 
response relationship.  This Bayesian model averaging approach is the Bayesian analog of the 
MCP-MOD methodology (Bretz et al., 2005), and “the Qualification of the MCP-Mod 
procedure” (FDA, 2015) is supportive in the use of MCP-MOD or Bayesian model averaging to 
assist in dose selection decisions. 
Bayesian model averaging is a general mixture distribution, where each mixture component is a 
different parametric model.  Prior weights are placed on each model and the posterior model 
weights are updated based on how well each model fits the data. Let 𝜇(𝑑) represent the mean of 
the dose response curve at dose 𝑑, 𝑦= {𝑦1, … , 𝑦𝑛} be the observed data, and 𝑚∈{1, … , 𝑀} be 
an index on the 𝑀 parametric models described below.  Then the posterior of the dose response 
curve, 𝜇(𝑑), of the Bayesian model averaging model is 
𝑝( 𝜇(𝑑) ∣𝑦) = ∑𝑝(𝜇(𝑑) ∣𝑦, 𝑚)
𝑀
𝑚=1
𝑝( 𝑚∣𝑦) 
𝑝( 𝑚∣𝑦) =
𝑝( 𝑦∣𝑚)𝑝(𝑚)
∑
𝑝( 𝑦∣𝑚∗)𝑝(𝑚∗)
𝑚∗
 
where 𝑝( 𝜇(𝑑) ∣𝑦, 𝑚) is the posterior mean dose response curve from model 𝑚, 𝑝( 𝑚∣𝑦) is the 
posterior weight of model 𝑚, 𝑝( 𝑦∣𝑚) is the marginal likelihood of the data under model 𝑚, 
and 𝑝(𝑚) is the prior weight assigned to model 𝑚.  In cases where 𝑝( 𝑦∣𝑚) is difficult to 
compute, Gould (2019) propose using the observed data’s fit to the posterior predictive 
distribution as a surrogate in calculating the posterior weights; this is the approach used in this 
analysis. 
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4.3.3.1. 
BMA Analysis and Reporting 
BMA will be executed for the proportion of participants who achieve clinical remission at Week 
12. 
BMA analysis will be summarized by dose and provide 
 Observed response 
 BMA estimated 
o Mean response  
o Standard error and standard deviation of the mean response 
o 2.5% and 97.5% quantiles 
o Summaries of posterior probability of LY - PBO treatment effect, i.e.,  
Pr(LY – PBO > EOI) where EOI is effect of interest 
 Plot that includes observed response, BMA estimated response, 2.5% and 97.5% 
posterior quantiles 
BMA analysis will be summarized by component and model parameter and provide 
 Posterior mean 
 Standard error and standard deviation of the posterior mean 
 2.5% and 97.5% posterior quantiles of the posterior distribution  
 Convergence diagnostics 
 Effective sample size 
 Prior distributions 
 Plot of the fitted BMA 
 Plot of the BMA components 
4.4. 
Secondary Endpoints Analyses 
4.4.1. 
Secondary Efficacy Endpoints 
4.4.1.1. 
Definition of Endpoints 
In the analyses of secondary efficacy outcomes, no adjustments for multiple testing will be 
performed unless otherwise specified. 
The efficacy assessments of secondary endpoints are shown in the following table: 
Table KFAH.3. 
Efficacy Assessments 
Clinical Remission 
SF subscore = 0, or SF = 1, and RB subscore = 0, and ES = 0 or 1, 
excluding friability. 
Clinical Response 
A decrease in the MMS of ≥2 points and ≥30% decrease from 
baseline, and a decrease of ≥1 point in the RB subscore from 
baseline or a RB score 0 or 1. 
Endoscopic Remission 
Mayo ES = 0 or 1, excluding friability. 
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Endoscopic Response 
A decrease in the Mayo ES of ≥1 point compared to baseline. 
Symptomatic Remission 
SF = 0, or SF = 1 with a decrease of ≥1 point from baseline, and 
RB = 0. 
Symptomatic Response 
≥30% decrease from baseline in the composite clinical endpoint 
of the sum of SF and RB subscores. 
Histologic Remission 
Geboes score <2 or Geboes subscores = 0 for Grade 2a, 2b, 3, 4, 
and 5. 
Histologic-Endoscopic 
Mucosal Healing 
Geboes scroe <2 and endoscopic remission. 
Abbreviations: ES = endoscopic subscore; MMS = modified Mayo score; RB = rectal bleeding; SF = stool 
frequency. 
4.4.1.2. 
Secondary Efficacy Endpoints for the Induction Period 
Secondary efficacy endpoints for the induction dosing period for participants who have not 
permanently discontinued at Week 12 and have achieved at Week 12 include clinical response, 
endoscopic remission, endoscopic response, symptomatic remission, symptomatic response, 
histologic remission, and histologic-endoscopic mucosal healing at Week 12. 
Analyses will be performed as per the methodology described in Section 4.1.1. 
The mITT population will be used for the secondary efficacy outcome analyses. 
4.4.1.3. 
Secondary Efficacy Endpoints for the Maintenance Period 
Secondary efficacy endpoints for the maintenance period for participants who were responder 
per IWRS at Week 12, have not permanently discontinued at Week 52, and have achieved at 
Week 52 include clinical remission, clinical response, endoscopic remission, endoscopic 
response, symptomatic remission, symptomatic response, histologic remission, and histologic-
endoscopic mucosal healing at Week 52. 
Analyses will be performed as per the methodology described in Section 4.1.1. 
The mITT population will be used for the secondary efficacy outcome analyses. 
4.4.2. 
Secondary Health Outcome Endpoints 
The following are patient-reported outcome instruments collected using a participant eDiary: 
 
Rectal Bleeding 
 
Stool Frequency 
 
Nocturnal Stool  
 
Bristol Stool Scale 
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 
Urgency NRS 
 
Abdominal Pain NRS 
 
Fatigue NRS, and 
 
PGR-S 
The following are patient-reported outcome instruments collected electronically: 
 
PGI-C and 
 
IBDQ 
Where appropriate, the total scores and sub-totals for individual dimensions collected will be 
summarized with means and 95% CIs by time point and by treatment group. The summary table 
will also include the change from baseline scores wherever applicable. The mean raw scores and 
mean change from baseline scores with corresponding 95% CIs will be presented graphically by 
treatment group and in a longitudinal fashion. 
The ITT population will be used for all health outcome analyses 
Mean change from baseline will be summarized by treatment group. 
4.4.3. 
Bioanalytical and Pharmacokinetic/Pharmacodynamic Methods 
PK/PD analyses to address secondary and exploratory objectives of this study will be described 
by Lilly in separate PK/PD analysis plans. Conduct of the PK/PD analyses will be the 
responsibility of Eli Lilly and Company.  
The PK/PD analyses will be initiated up to approximately three weeks before the planned 
database lock dates. All analyses will be performed by unblinded Lilly PK personnel, who are 
unblinded to subject treatment assignments to support dose adjustments. Results from the PK/PD 
analyses will not be shared with site or blinded study team personnel prior to the respective 
database lock. 
4.5. 
Tertiary/Exploratory Endpoints Analyses 
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4.6. 
Safety Analyses 
All safety data will be descriptively summarized by treatment groups and analyzed based on the 
safety population as defined in Section 3.  The safety analyses include AEs, safety in special 
groups and circumstances, including Adverse Events of Special Interest (AESI), laboratory 
analytes, QIDS-SR16, C-SSRS, ECGs, and vital signs.  The duration of exposure will also be 
summarized.  The categorical safety measures will be summarized using incidence rates and 
analyzed by Fisher’s exact test.  The mean change in the continuous safety measures including 
vital signs, QIDS-SR16, physical characteristics, and laboratory values will be summarized by 
visits and analyzed by ANCOVA, with treatment and baseline values in the model.  More details 
are provided in subsequent sections.   
For specific events of special interest (see Section 4.6.3 for more details), an incidence rate, IR 
per 100 patient-years of observation (PYO), will be provided.  Patient-years of observation will 
be calculated as the sum of all patient observation time in the treatment group.  For a patient with 
an event, the observation time will be censored at the event date; for a patient without the event, 
the observation time will be counted until the patient’s last treatment dose date plus 30 days or 
the patient’s last visit, whichever occurs first. Only events that occur within 30 days after the 
patient’s treatment discontinuation date will be considered. 
See formula as follows: 
𝑃𝑌𝑂=
∑
𝑒𝑣𝑒𝑛𝑡 𝑠𝑡𝑎𝑟𝑡 𝑑𝑎𝑡𝑒−𝑓𝑖𝑟𝑠𝑡 𝑡𝑟𝑡 𝑑𝑜𝑠𝑒 𝑑𝑎𝑡𝑒+ 1 
365.25 
𝑝𝑡 𝑤 𝑒𝑣𝑒𝑛𝑡
+
∑
𝑙𝑎𝑠𝑡 𝑜𝑏𝑠𝑒𝑟𝑣𝑎𝑡𝑖𝑜𝑛 𝑑𝑎𝑡𝑒−𝑓𝑖𝑟𝑠𝑡 𝑡𝑟𝑡 𝑑𝑜𝑠𝑒 𝑑𝑎𝑡𝑒+ 1 
365.25 
𝑝𝑡 𝑤/𝑜 𝑒𝑣𝑒𝑛𝑡
 
 
Incidence rate will be calculated as follows:   
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𝐼𝑅= 𝑢𝑛𝑖𝑞𝑢𝑒 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑝𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑤𝑖𝑡ℎ 𝑒𝑣𝑒𝑛𝑡 
𝑃𝑌𝑂
x100 
For each IR provided, a 95% CI will be calculated based on the Poisson distribution.  Treatment 
group comparisons based on IR will be provided based on the incidence rate difference (IRD) 
together with its 95% CI.   
Not all displays described in this section will necessarily be included in the CSRs. Any display 
described and not provided in the CSR would be available upon request. Not all displays will 
necessarily be created as a “static” display. Some may be incorporated into interactive display 
tools instead of or in addition to a static display. Any display created interactively will be 
included in the CSR if deemed relevant to the discussion. 
4.6.1. 
Extent of Exposure 
Duration of exposure to study treatment (defined as time since first injection of study treatment 
in days) will be summarized by treatment group during the Induction Period, the Maintenance 
Period, and the Extension Period. 
Duration of exposure during the Induction Period for the Safety Population will be calculated as: 
(Disposition date (for those who have discontinued the Induction Period), OR 
Maintenance/Extension Start date -1 (for those who have completed the Induction Period), OR 
Date of last study visit in the Induction Period (for those who are still being treated in the 
Induction Period) – Date of first injection of study treatment + 1) 
Duration of exposure during the Maintenance Period will be calculated as: 
(Disposition date (for those who have discontinued the Maintenance Period), OR Date of last 
study visit in the Maintenance Period (for those who are still being treated in the Maintenance 
Period) – Date of the Visit 10 injection of study treatment + 1) 
Duration of exposure to LY3471851 during the Extension Period will be calculated as: 
(Disposition date (for those who have discontinued the Extension Period), OR Date of last study 
visit in the Extension Period (for those who are still being treated in the Extension Period) – 
Date of the Visit 10 injection of study treatment + 1) 
Duration of exposure to LY3471851 for the combined Induction Period and Maintenance Period 
will be calculated as: 
(Disposition date (for those who have discontinued the Maintenance Period), OR Date of last 
study visit in the Maintenance Period (for those who are still being treated in the Maintenance 
Period)– Date of first injection of LY3471851 + 1) 
Duration of exposure to LY3471851 for the combined Induction Period and Extension Period 
will be calculated as: 
(Disposition date (for those who have discontinued the Extension Period), OR Date of last study 
visit in the Extension Period (for those who are still being treated in the Extension Period)– Date 
of first injection of LY3471851 + 1) 
The date of first injection of LY3471851 is defined in Table KFAH.4Error! Reference source 
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Table KFAH.4. 
First Injection of LY3471851 by Treatment Group 
 
Visit of first LY3471851 
All patients randomized to LY3471851 
(regardless of Week 12 response status) 
Week 0 (Visit 2) 
Week 12 Inadequate Responders originally 
randomized to placebo and assigned to 
LY3471851 at Visit 10 
Week 14 (Visit 10) 
Descriptive statistics (n, mean, SD, minimum, first quartile, median, third quartile, and 
maximum) will be provided for patient-days of exposure and the frequency of patients falling 
into different exposure ranges will be summarized.  Exposure ranges are as follows:   
 >0, ≥4 weeks, ≥12 weeks, and ≥52 weeks. 
 >0 to <4 weeks, ≥4 weeks to <12 weeks, ≥12 weeks to <52 weeks, and ≥52 weeks.  
Additional exposure ranges may be considered if necessary.  
A by-patient listing of exposure duration will be provided. 
Patients who had dose modification will be grouped under the randomized treatment arm and 
will not be grouped by the modified dose amount. 
No inferential analysis for comparison between treatment arms will be performed. 
4.6.2. 
Adverse Events 
4.6.2.1. 
Adverse Events 
Adverse events are recorded in the eCRF.  Each AE will be coded to SOC and PT, using the 
Medical Dictionary for Regulatory Activities (MedDRA) version that is current at the time of 
database lock.  Severity of AEs is recorded as mild, moderate, or severe.   
Treatment-emergent adverse events (TEAEs) are defined as events that either first occurred or 
worsened in severity after the first dose of study drug and the earliest of the visit study drug 
disposition date or the last visit date during the treatment period, whichever occurred first, and 
up to 30 days after study treatment discontinuation.  The MedDRA Lowest Level Term (LLT) 
will be used in defining which events are treatment-emergent.  The maximum severity for each 
LLT during the baseline period until the first dose of the study medication will be used as 
baseline.  If an event is preexisting during the baseline period, but it has missing severity, and the 
event persists during the treatment period or up to 30 days after treatment discontinuation, then 
the baseline severity will be considered mild for determining any postbaseline treatment-
emergence (i.e., the event is treatment-emergent unless the severity is coded mild at 
postbaseline).  If an event occurring postbaseline has a missing severity rating, then the event is 
considered treatment-emergent.  Should there be insufficient data for an AE start date to make 
this comparison (e.g., the AE start year is the same as the treatment start year, but the AE start 
month and day are missing), the AE will be considered treatment-emergent.  For events 
occurring on the day of the first dose of study treatment, the day of the onset of the event will 
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both be used to distinguish between pretreatment and posttreatment in order to derive treatment-
emergence. 
In general, summaries will include the number of patients in the safety population (N), frequency 
of patients experiencing the event (n), and relative frequency (i.e., percentage; n/N*100).   
In an AE overview table, the number and percentage of patients in the safety analysis set who 
experienced death, a serious adverse event (SAE), any TEAE, permanent discontinuation from 
study drug due to an AE, or a severe TEAE will be summarized by treatment group.   
The number and percentage of patients with TEAEs will be summarized by treatment group in 
2 formats listed below.  For events that are gender specific, the denominator and computation of 
the percentage will only include patients from the given gender. 
 by MedDRA PT nested within SOC with SOCs ordered alphabetically, and events 
ordered within each SOC by decreasing frequency in the LY3471851 1800µg treatment 
group. 
 by MedDRA PT with events ordered by decreasing frequency in the LY3471851 1800µg 
treatment group. 
Adverse events leading to permanent discontinuation of study drug and AEs leading to 
temporary interruption of study drug will also be summarized by treatment group using 
MedDRA PT nested within SOC.  Events will be ordered by decreasing frequency within SOC in 
the LY3471851 1800µg treatment group. 
A summary of temporary interruptions of study drug will also be provided, showing the number 
of patients who experienced at least 1 temporary interruption and the number of temporary 
interruptions per patient with an interruption.  Further, the duration of each temporary 
interruption (in days) and the cumulative duration of dose interruption (in days) using basic 
descriptive statistics (n, mean, SD, minimum, first quartile, median, third quartile, and 
maximum) will be displayed. 
Common TEAEs are defined as TEAEs that occurred in ≥1% (before rounding) of patients in 
any treatment group including placebo.  The number and percentage of patients with common 
TEAEs will be summarized by treatment using MedDRA PT ordered by decreasing frequency in 
the LY3471851 1800µg treatment group. 
The number and percentage of patients with TEAEs will be summarized by maximum severity 
by treatment using MedDRA PT ordered by decreasing frequency for the common TEAEs.  For 
each patient and TEAE, the maximum severity for the MedDRA level being displayed is the 
maximum postbaseline severity observed from all associated LLTs mapping to that MedDRA 
PT.   
4.6.2.2. 
Serious Adverse Events 
An individual listing of all AEs including preexisting conditions will be provided.  A separate 
listing will include AEs that led to permanent discontinuation from the study drug.  In addition, a 
listing of AEs that occur more than 30 days after study treatment discontinuation will be 
provided. 
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With the International Conference on Harmonisation (ICH) E2A guideline, a SAE is any AE that 
results in 1 of the following outcomes: 
 death 
 initial or prolonged inpatient hospitalization 
 a life-threating experience (that is, immediate risk of dying) 
 persistent or significant disability/incapacity 
 congenital anomaly/birth defect 
 considered significant by the investigator for any other reason 
The number and percentage of patients who experienced any ICH-defined SAE will be 
summarized by treatment group during the treatment and follow-up periods using MedDRA PT 
nested within SOC.  Events will be ordered by decreasing frequency within SOC in the 
LY3471851 1800µg treatment group.  In addition, the SAEs will be summarized by treatment 
group using MedDRA PT without SOC.  An individual listing of all SAEs will be provided. 
4.6.3. 
Adverse Events of Special Interest 
4.6.3.1. 
Infections 
Infections will be defined using  all PTs from the MedDRA Infections and Infestations SOC.  
Serious infection will be defined as all the infections that meet the SAE criteria.   
The number and percentage of patients with TEAEs of infections, serious infections, and 
infections resulting in study drug discontinuation will be summarized by treatment group using 
MedDRA PTs.   
The number and percentage of patients with TEAEs of infections by maximum severity will be 
summarized by treatment group using MedDRA PTs.   
For infections of special interest (serious infections, potential opportunistic infections [POIs], 
herpes zoster, and herpes simplex), the IR (for detail, see Section 4.6) and 95% CI will be 
calculated.   
Treatment-emergent infectious events will be reviewed in context of other clinical and laboratory 
parameters. A listing of patients experiencing treatment-emergent infectious AEs will be 
provided.  The listing will include patient demographics, treatment group, treatment start and 
stop dates, infectious event, event start and stop dates, total leukocytes, total lymphocytes, 
absolute neutrophils, event seriousness, and event outcome. 
The infectious TEAE will be further analyzed in terms of potential opportunistic infection, 
herpes zoster, and herpes simplex.  A summary of hepatitis B virus (HBV) deoxyribonucleic acid 
(DNA) monitoring results and association between infection and neutropenia/lymphopenia will 
also be provided in the context of infections.   
Potential Opportunistic Infections 
Potential opportunistic infections will be identified according to 2 different approaches.   
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First, POIs will be identified from TEAEs based on a Lilly-defined list of MedDRA PTs shown 
in 6.8. These PTs are a subset of terms from the Infections and Infestations SOC.   
Second, a list of all the infection details captured from the infection-specific eCRF (including 
primary/secondary infecting organism and infection site) will be provided.  Of note, the infecting 
organism that was entered as free text by the investigator (instead of as a selection from the pull-
down list) will also be provided.   
The summary analysis of POIs identified using the 2 approaches above will be provided.  Each 
case meeting the case definition for an opportunistic infection will be summarized by PT nested 
under infection pathogen.  Events will be ordered by decreasing frequency of pathogen nested 
under pathogen species (mycobacteria, bacteria, fungal, viral, parasites).  The order of frequency 
will be determined using the LY3471851 1800µg group. 
Potential opportunistic infections identified through these approaches will be combined in 1 list 
for medical assessment for final classification of whether the case definition was met according 
to the consensus paper after database lock (i.e., Winthrop 2015).  An additional summary may be 
conducted based on medical assessment.   
Herpes Zoster 
A summary table of herpes zoster will be provided.  Herpes zoster will be defined based on the 
MedDRA PTs as listed under Herpes zoster (any form) (II) in 6.8, excluding Varicella virus text 
(10070444).  The summary table will also include event maximum severity, seriousness, whether 
resulting in temporary study drug interruption, whether resulting in study drug discontinuation, 
whether treated with antiviral medication, and event outcome.   
If a patient has more than 1 event of herpes zoster, the event with the maximum severity will be 
used in these summary tables.  If more than 1 event of herpes zoster occurs with the same 
severity, the event with the longest duration will be used in the summary table. 
Herpes Simplex 
A summary analysis of herpes simplex will be provided.  Herpes simplex will be defined based 
on the MedDRA PTs as listed under Herpes simplex (invasive disease only) (IV) in 6.8.  The 
summary table will include event maximum severity, seriousness, whether resulting in temporary 
study drug interruption, whether resulting in study drug discontinuation, and whether treated 
with antiviral medication.  Antiviral medication will be selected based on ATC code level 2 
“antiviral for systemic use.” 
If a patient has more than 1 event of herpes simplex, the event with the maximum severity will 
be used in these summary tables.  If more than 1 event of herpes simplex occurs with the same 
severity, the event with the longest duration will be used in the summary table. 
HBV DNA 
A listing of patients with detectable HBV DNA will be provided. 
HBV DNA status (not detectable, detectable but not quantifiable [ie, <29 IU/mL], quantifiable 
[ie, ≥29 IU/mL]) will be summarized by treatment group stratified by baseline HBV serology 
status, specifically: 
 HBsAb- / HBcAb- 
 HBsAb+ / HBcAb- 
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 HBsAb+ / HBcAb+ 
 HBsAb- / HBcAb+ 
Association between Infection and Neutropenia/Lymphopenia 
To evaluate the association between infection and neutropenia and also between infection and 
lymphopenia, the frequency of infections will be provided by the worst Common Terminology 
Criteria for Adverse Events (CTCAE) grades of neutropenia and lymphopenia, respectively.  
Infection outcomes considered for this analysis are any treatment-emergent infection, serious 
infection, and herpes zoster.  For this analysis, no statistical comparison will be provided.  
In addition, a summary table will be provided for treatment-emergent infections that were 
preceded or accompanied by neutropenia/lymphopenia.  For this analysis, neutropenia is defined 
as CTCAE Grade 2 or greater.  Infection events with onset date ≤14 days before or after the 
Grade 2 neutrophil/lymphocyte count collection date will be considered as infections preceded or 
accompanied by neutropenia. 
4.6.3.2. 
Systemic Hypersensitivity Reactions (including cytokine release syndrome) 
A search will be performed using the current MedDRA version Standardised MedDRA Queries 
(SMQs) to search for relevant events, using the following queries: 
 Anaphylactic reaction SMQ (20000021) 
 Hypersensitivity SMQ (20000214) 
 Angioedema SMQ (20000024) 
Events that satisfy the queries will be listed, by temporal order within patient ID, and will 
include SOC, PT, SMQ event categorization including detail on the scope (narrow or broad), 
reported AE term, AE onset and end dates, severity, seriousness, outcome, etc. 
4.6.3.3. 
Malignancies 
Malignancies will be identified using terms from the malignant tumors SMQ (SMQ 20000194).  
Malignancies excluding nonmelanoma skin cancers (NMSC) and NMSC will be reported 
separately. 
A listing including all malignancy cases will be provided.  An NMSC flag will be provided using 
the following MedDRA PTs (the list will be updated depending on the MedDRA version used 
for analysis):   
 Squamous cell carcinoma of skin (10041834)  
 Bowen’s disease (10006059) 
 Basal cell carcinoma (10004146) 
 Basosquamous carcinoma (10004178) 
 Basosquamous carcinoma of skin (10004179) 
 Squamous cell carcinoma (10041823) 
 Skin squamous cell carcinoma metastatic (10077314) 
 Skin cancer (10040808) 
 Carcinoma in situ of skin (10007390) 
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The number and percentage of patients with TEAE-associated malignancies excluding NMSC 
and NMSC will be summarized by treatment group.  In addition, the IR (for detail, see Section 
4.6) and 95% CI will be calculated for the overall observation time.  All cases identified by 
malignant tumors SMQ will be assessed after database lock by the medical team to determine (1) 
confirmed NMSC cases and (2) symptom and date that triggered the malignancy investigation or 
diagnosis.  An additional listing based on medical review may also be provided if deemed 
necessary.  All cases reported in the study database or by Lilly Safety System (LSS) report, 
disregarding the length of gap between the last treatment dose date and the event date will be 
included.   
4.6.3.4. 
Gastrointestinal Perforations 
Treatment-emergent adverse events potentially related to gastrointestinal (GI) perforations will 
be analyzed using reported AEs.  Identification of these events will be based on the PTs of the 
MedDRA Gastrointestinal Perforations SMQ (SMQ 20000107); note that this SMQ holds only 
narrow terms and has no broad terms.  Potential GI perforations identified by the above SMQ 
search will be provided as a listing for internal review by the medical safety team.  Each case 
will be assessed to determine whether it is a GI perforation.  Frequency and relative frequency 
for each PT will be provided, ordered by decreasing frequency in the LY3471851 1800µg 
treatment group.  Comparisons between each LY3471851 treatment group and placebo will be 
made using Fisher’s exact test. 
4.6.4. 
Injection Site Reaction 
If a participant spontaneously reports symptoms of an injection site reaction, an authorized 
member of the site staff who, in the opinion of the investigator, is qualified to assess reports of 
potential ISRs and who is not involved with any other study procedure will evaluate the 
participant’s report. 
The number and percentage of patients who experienced ISR will be summarized by treatment 
group and by visit. The number and percentage of patients with the following ISR records will be 
summarized by treatment group and by visit. Details about ISR records are referred to the Case 
Report Form (CRF). 
 Anatomical location of the injection site reaction 
 Abdomen Side 
 Directionality of the anatomical location of the administration 
 Arm side 
 Whether the subject has any injection site erythema (reddening) or not 
 Severity of the injection site erythema 
 Whether the subject has any injection site induration (hardening or thickening of tissue) 
or not 
 Severity of the injection site induration 
 Whether the subject has any injection site pain (including burning) or not 
 Severity of the injection site pain 
 Whether the subject has any injection site pruritus 
 Severity of the injection site pruritus 
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 Whether the subject has any injection site edema (swelling or accumulation of fluid in 
tissues at height above normal skin) or not 
 Severity of the injection site edema 
 When the Injection related event occurred in relationship to the study treatment 
Ordinal logistic regression will be used for the ordinal ISR reported. The frequency of the 
maximum severity of ISRs will be summarized by treatment group. 
4.6.5. 
Clinical Laboratory Evaluation 
Laboratory evaluations will be summarized and analyzed for the following periods: 
 Induction Period, 
 Maintenance Period,  
 Extension Period (including Extension Induction and Extension Maintenance) 
All laboratory tests will be presented using the Système International of units (SI) and 
conventional (CN) units.  For topics of safety in special groups and circumstances, laboratory 
test units will be specified for each analysis. 
Lilly Large Clinical Trial Population Based (LCTPB) reference limits will be used to define the 
low and high limits because it is generally desirable for limits used for analyses to have greater 
specificity (identify fewer false positive cases) than reference limits used for individual patient 
management.  When Lilly LCTPB reference ranges are unavailable, then central laboratory 
(Labcorp) reference ranges will be used.  For the 4 key hepatic laboratory assessments (alanine 
aminotransferase [ALT], aspartate aminotransferase [AST], total bilirubin, and alkaline 
phosphatase [ALP]), central laboratory reference ranges (Labcorp) will be used and all results 
pertaining to these assessments will be included as a separate analysis to address the risk of liver 
injury as a special safety topic (see Section 4.6.3.1).  Central laboratory reference ranges 
(Labcorp) will also be used to evaluate immunoglobulins and lymphocyte cell subsets (see 
Sections 4.6.5.2 and 4.6.5.6).  See 6.10 for details of the reference range by laboratory analytes.   
The low-density lipoprotein/high-density lipoprotein (LDL/HDL) ratio will be derived as the 
ratio of LDL cholesterol to HDL cholesterol.  There are no Lilly LCTPB reference ranges or 
central lab reference ranges for the LDL/HDL ratio.   
The following will be conducted for laboratory analyte measurements collected quantitatively: 
 Box plots for observed values:  Values at each visit (starting at randomization) and 
change from baseline to each visit and to last postbaseline measure will be displayed in 
box plots for patients who have a baseline and at least 1 postbaseline visit.  For visits 
included in the treatment period, patients will be included only if the visit occurs on or 
before the date of treatment discontinuation/completion.  Follow-up visit will be the first 
visit that occurred during the Follow-up period.  Individual measurements outside of 
reference limits will also be displayed using distinct symbols overlaying the box plot.  
Original-scale data will be used for the display but for some analytes (e.g., 
immunoglobulins) a logarithmic scale will be used to aid in viewing the measures of 
central tendency and dispersion.  Unplanned measurements will be excluded.  Descriptive 
summary statistics will be included in a table below the box plot.  These box plots will be 
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used to evaluate trends over time and to assess a potential impact of outliers on central 
tendency summaries.  A p-value for change from baseline to endpoint will be provided 
using an ANCOVA model with explanatory term for treatment and the baseline value as 
a covariate.  Endpoint will be the last observation where patient is on treatment.   
 Treatment-emergent high/low analyses:  The number and percentage of patients with 
treatment-emergent high and low laboratory results at any time will be summarized by 
treatment group.  Planned and unplanned measurements will be included.  A treatment-
emergent high result is defined as a change from a value less than or equal to the high 
limit at all baseline visits to a value greater than the high limit at any time during the 
treatment period and up to 60 days after treatment discontinuation.  A treatment-emergent 
low result is defined as a change from a value greater than or equal to the low limit at all 
baseline visits to a value less than the low limit at any time during the treatment period 
and up to 60 days after treatment discontinuation.  The Fisher’s exact test will be used for 
the treatment comparisons. 
For laboratory analyte measurements collected qualitatively, a listing of abnormal findings will 
be created. The listing will include patient ID, treatment group, laboratory collection date, 
analyte name, and analyte finding. 
4.6.5.1. 
Abnormal Hepatic Tests 
Analyses for abnormal hepatic tests involve 4 laboratory analytes:  ALT, AST, total bilirubin, 
and ALP.  Analyses for the change from baseline to last visit that occurred on or before the date 
of treatment discontinuation and shift tables are described in Section 4.6.5.  This section 
describes additional analyses for the topic.  The central laboratory reference ranges (Labcorp) 
will be used for ALT, AST, total bilirubin, and ALP hepatic laboratory assessments. 
The number and percentage of patients with the following abnormal elevations in hepatic 
laboratory tests at any time up to 60 days after treatment discontinuation will be summarized by 
treatment group. LY3471851 groups will be compared to placebo using Fisher’s exact text: 
 The percentages of patients with an ALT measurement ≥3×, 5×, and 10× the 
central laboratory upper limit of normal (ULN) during the treatment and 
follow-up periods will be summarized for all patients with a postbaseline 
value.  
 The percentages of patients with an AST measurement ≥3×, 5×, and 10× the 
central laboratory ULN during the treatment and follow-up periods will be 
summarized for all patients with a postbaseline value. 
 The percentages of patients with a total bilirubin measurement ≥2 × the 
central laboratory ULN during the treatment period will be summarized for all 
patients with a postbaseline value. 
 The percentages of patients with an ALP measurement ≥3× the central 
laboratory ULN during the treatment and follow-up periods will be 
summarized for all patients with a postbaseline value. 
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Second, to further evaluate potential hepatotoxicity, an Evaluation of Drug-Induced Serious 
Hepatotoxicity (eDISH) plot will be created for all patients whether treated with LY3471851 
and/or other treatment using the whole study and follow-up periods.  Each patient with at least 1 
postbaseline ALT and total bilirubin will be included in the eDISH.  The points correspond to 
maximum total bilirubin and maximum ALT, even if not obtained from the same blood draw.  A 
listing of patients potentially meeting Hy’s rule will be provided (defined as greater than or equal 
to 3× ULN for ALT or AST, and greater than or equal to 2× ULN for total bilirubin, not 
necessarily at the same time). 
Third, a listing will be provided to the medical safety team for internal review according to the 
following SMQs:   
 Broad and narrow terms in the Liver-related investigations, signs and symptoms SMQ 
(SMQ 20000008) 
 Broad and narrow terms in the Cholestasis and jaundice of hepatic origin SMQ 
(SMQ 20000009) 
 Broad and narrow terms in the Hepatitis non-infectious SMQ (SMQ 20000010) 
 Broad and narrow terms in the Hepatic failure, fibrosis and cirrhosis and other liver 
damage-related conditions SMQ (SMQ 20000013)  
 Narrow terms in the Liver-related coagulation and bleeding disturbances SMQ 
(SMQ 20000015). 
4.6.5.2. 
Lymphocyte Subset Cell Counts 
The following lymphocyte subsets will be analyzed: 
CD3+ T Cells – % 
CD3+ T Cells – Absolute 
CD3+CD8+ T cells (CD8) – % 
CD3+CD8+ T cells (CD8) – Absolute 
CD3+CD4+ T cells (CD4) – % 
CD3+CD4+ T cells (CD4) – Absolute 
CD56+/CD16+ NK cells – % 
CD56+/CD16+ NK cells – Absolute 
CD19+ B cells – % 
CD19+ B cells – Absolute 
CD4/CD8 Ratio – Calculated 
CD3+4+8+ % 
CD3+4+8+ Abs 
CD3/CD19 Ratio - Calculated 
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For each type of cells, both the absolute count and the relative count (i.e., as a percentage of the 
total lymphocyte population) will be analyzed.  In addition, the ratio of CD4 cell counts to CD8 
cell counts will be analyzed.   
The analyses for these parameters will be performed using the same approaches as described for 
analysis of clinical laboratory measurements in Section 4.6.5.  For determining treatment-
emergent abnormal, high, or low lymphocyte subset cell counts, central laboratory reference 
ranges (Labcorp) will be used when available; note that reference ranges are available only for 
some of the lymphocyte subset cell count analytes. 
4.6.5.3. 
Lipids Effects 
Analyses for the change from baseline to last observation, and shift tables in total cholesterol, 
LDL cholesterol, HDL cholesterol, and triglycerides are described in Section 4.6.5.   
Treatment-emergent adverse events potentially related to hyperlipidemia will also be analyzed, 
based on reported AEs.  The target surveillance term “Hyperlipidemia” is a Lilly-defined 
MedDRA search criteria list that is a subset of the PTs in the MedDRA SMQ “Dyslipidemia” 
that are related to elevated or increased lipids.  MedDRA PTs, each with a narrow scope from the 
SMQ, for the target surveillance term are shown in 6.9.  Frequency and relative frequency for 
each PT will be provided, ordered by decreasing frequency in the LY3471851 1800µg treatment 
group.   
4.6.5.4. 
Renal Function Effects 
Effects on renal function will be assessed through analyses of creatinine, which are described in 
Section 4.6.5.   
4.6.5.5. 
Elevations in Creatine Phosphokinase 
Analyses of creatine phosphokinase are described in Section 4.6.5.  
4.6.5.6. 
Serum Immunoglobulin Concentrations 
Each serum Ig concentration (IgA, IgG, and IgM) will be analyzed.  The analyses for these 
parameters will be performed using the same approaches as described for analysis of clinical 
laboratory measurements in Section 4.6.5.  For determining treatment-emergent abnormal, high, 
or low serum Ig concentrations for IgA, IgG, and IgM, central laboratory reference ranges 
(Labcorp) will be used. 
4.6.6. 
Vital Signs and Other Physical Characteristics 
Vital signs and physical characteristics include systolic blood pressure (SBP), diastolic blood 
pressure (DBP), pulse, weight, BMI, and body temperature.  Original-scale data will be 
analyzed.  When these parameters are analyzed as continuous numerical variables, unplanned 
measurements will be excluded.  When these parameters are analyzed as categorical outcomes, 
planned and unplanned measurements will be included.   
Vital signs and physical characteristics will be summarized and analyzed for the following 
periods: 
 Induction Period 
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 Maintenance Period  
 Extension Period  
The planned analyses described for the laboratory analytes in Section 4.6.5 will be used to 
analyze the vital signs and physical characteristics. 
Table KFAH.5 defines the low and high baseline values as well as the criteria used to define 
treatment-emergence based on postbaseline values.  Postbaseline values include all values after 
baseline in the treatment and follow-up periods.  The blood pressure and pulse rate criteria are 
consistent with the document Selected Reference Limits for Blood Pressure, Orthostasis, and 
ECG Numerical Parameters (Including Heart Rate) for Use in Phase II-IV Clinical Trials 
Version 1.1 approved on 8 March 2013 as recommended by the Lilly Cardiovascular Safety 
Advisory Committee (CVSAC). 
Table KFAH.5. 
Categorical Criteria for Abnormal Treatment-Emergent Blood Pressure and Pulse Measurement, and 
Categorical Criteria for Weight Changes for Adults 
Abbreviation:  mm Hg = millimeters of mercury. 
4.6.7. 
Electrocardiograms 
Detailed Electrocardiogram results are part of the clinical database for this study. Should an ECG 
be performed in association with an AE or medical history event, the occurrence of the ECG 
(“Yes/No”) will be provided in a by-patient listing.  
If any clinically significant ECG measurement occurs, this will be recorded as an AE. ECG data 
will not be analyzed. 
Low 
High 
Systolic Blood 
Pressure (mm Hg) 
≤90 (low limit) and decrease from 
lowest value during baseline ≥20 if 
>90 at each baseline visit 
≥140 (high limit) and increase from highest 
value during baseline ≥20 if <140 at each 
baseline visit 
Diastolic Blood 
Pressure (mm Hg) 
≤50 (low limit) and decrease from 
lowest value during baseline ≥10 if 
>50 at each baseline visit 
≥90 (high limit) and increase from highest 
value during baseline ≥10 if <90 at each 
baseline visit 
Pulse  
(beats per minute)  
<50 (low limit) and decrease from 
lowest value during baseline ≥15 if 
≥50 at each baseline visit 
>100 (high limit) and increase from highest 
value during baseline ≥15 if ≤100 at each 
baseline visit 
Weight 
(kilograms) 
(Loss) decrease ≥7% from lowest 
value during baseline 
(Gain) increase ≥7% from highest value 
during baseline 
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4.6.9. 
Suicidal Ideation/Behavior and Depression 
During the study, suicidal ideation and behavior, and depression will be assessed prospectively 
by the investigator via signs and symptoms and through the use of the Columbia-Suicide 
Severity Rating Scale (C-SSRS) and the Quick Inventory of Depressive Symptomatology Self 
Report (QIDS-SR16). 
Analyses will include: 
 C-SSRS: Only a listing of the C-SSRS data will be provided. 
 QIDS-SR16: Shift table will be provided showing the number and percentage of patients 
within each baseline category (maximum value) versus each post-baseline category 
(maximum value) by treatment. Additionally, outcomes such as any increase in 
depression will be compared between treatments. 
4.7. 
Other Analyses 
4.7.1. 
Efficacy Subgroup Analysis 
Subgroup analyses will be conducted on the mITT population for the following: 
 Clinical remission  
 Clinical response  
 Endoscopic remission 
 Endoscopic response 
 Symptomatic remission 
 Symptomatic response 
 Histologic remission 
 Histologic-endoscopic mucosal healing 
The following subgroups (but not limited to only these) will be evaluated: 
 Gender 
 Age category 
 Body weight 
 Race 
 Geographic region 
 Baseline disease severity and activity 
 Duration and location of disease 
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 Previous systemic therapy 
 Previous advanced therapy, and 
 Concomitant therapy for UC. 
Descriptive statistics will be provided for each treatment and stratum of a subgroup as outlined, 
regardless sample size.  
Each categorical variable will be analyzed individually with a logistic regression model that 
contains the treatment, the subgroup variable, and subgroup by treatment interaction. The 
treatment-by-subgroup interaction will be tested at the 10% significant level. Within each 
subgroup category, the proportion of responders by treatment, treatment differences, and 95% 
CIs will be displayed.  
For continuous variables, MMRM analysis will be performed with subgroup-by-treatment 
interaction. Within each subgroup, LS means by treatment, LS mean differences, and 95% CIs 
will be displayed. 
If the number of patients in any subgroup category is less than 10% of the total population, only 
summaries of the efficacy data will be provided. Additional subgroup analyses may be 
performed as deemed necessary. 
4.7.2. 
Safety Subgroup Analyses 
Safety subgroup analysis for safety related endpoints will be performed within the context of the 
integrated safety analysis. No safety subgroup analysis will be performed specifically for this 
study unless there is a potentially relevant finding during the periodic study safety reviews. 
4.8. 
Interim Analyses  
Analyses for the primary database lock will be conducted when all participants have completed 
the Induction Period (that is, have completed the Week 12 visit) or else have discontinued study 
treatment. 
The following interim analyses may be conducted to assess the primary efficacy results: 
 for early termination assessment and decision when approximately 50 patients have either 
completed the dosing induction period or discontinued study treatment, 
 for early termination or Stage 2 dose decisions when approximately 100 patients have 
either completed the dosing induction period or discontinued study treatment, 
 for early trigger to Phase 3 assessment when approximately 150 patients have either 
completed the dosing induction period or discontinued study treatment, and 
 for Phase 3 study trigger when approximately 200 patients have either completed the 
dosing induction period or discontinued study treatment. 
Bayesian pairwise comparisons (LY3471851 dose to placebo) will be employed for potential 
decisions at each interim analysis using Bayesian posterior probability. Note that Stage 2 
treatment doses will be determined based on results of the second interim analysis and 
recommendations of the sponsor’s IAC. 
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The interim efficacy results will be used for internal decision making to terminate or trigger 
planning activities associated with the investigational product and to aid development of PK/PD 
modeling. Hence, there will be no alpha adjustment at the interim analyses. For each pairwise 
comparison at each interim analysis, a alpha of 0.05 will be used. The study may not be stopped 
for positive efficacy. The assessment will be conducted by a sponsor assessment committee with 
a limited number of pre-identified team members who do not have direct site contact or data 
entry/validation responsibilities. To minimize any bias being introduced into the analysis of the 
study results, the SAP and PK/PD analysis plan will be finalized and approved before the first 
efficacy interim analysis is initiated. 
Information that may unblind the study during the analyses will not be reported to study sites or 
the blinded study team until a decision is made to unblind the entire study team. 
Ongoing monitoring of safety data (including AEs, SAEs, and selected laboratory 
measurements) will be continued throughout the study using blinded data.   Reviewing details 
are specified in the trial level safety review (TLSR) plan or a separate document. 
4.8.1. 
Data Monitoring Committee (DMC) 
Not applicable. An assessment of unblinded interim data will be conducted by an internal 
assessment committee (IAC) with a limited number of prespecified team members who do not 
have direct site contact or data entry or validation responsibilities. An AC charter will provide 
details on AC membership and the governing processes.  
4.9. 
Changes to Protocol-Planned Analyses 
Protocol deviations will be identified throughout the study.  Important protocol deviations (IPDs) 
are defined as those deviations from the protocol that would potentially compromise patients’ 
safety, data integrity, or study outcome.   
A separate document known as the “The KFAH Trial Issues Management Plan” describes the 
categories and subcategories of important protocol deviations, whether or not these deviations 
are IPDPPs, and how the IPDs would be identified.  
The number and percentage of patients having IPDs will be summarized within category and 
subcategory of deviations by dosing regimen for the mITT population. 
 
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5. 
Sample Size Determination 
Approximately 200 participants, in total, may be randomized across all study stages. 
During Stage 1, approximately 100 participants will be randomized to a high dose (
 µg) of 
LY3471851, a lower (
 µg) dose of LY3471851, or placebo groups in a 2:2:1 ratio. 
During Stage 2, up to approximately 100 additional participants will be randomized. Stage 2 will 
have a placebo group and may have more LY3471851 treatment groups than Stage 1, or fewer, 
based on decisions taken after the last interim analysis of Stage 1.  
The power calculations for this study assume the following: 
 At end of study, three non-placebo treatment groups will have sample size of 
approximately either 40, 60, or 80 patients. 
 At end of study, the placebo group will have a sample size of approximately 40 patients. 
 For the sake of simplicity in the power calculation, it is assumed that there is no 
difference in treatment effect between advanced therapy-failed and conventional-failed 
patients. To simplify, it is also assumed that all treatment groups have the same treatment 
effect. 
 It is assumed that the true placebo response rate is approximately 5% and the true 
treatment response is approximately 35%. 
 Power is calculated for 3 hypothesis tests, 1 for each treatment group against placebo, and 
adjust for multiple comparisons using the conservative Bonferroni adjustment. Power is 
calculated using a family-wise error rate of α=.05. 
Given these assumptions, the power to reject the null hypotheses for the treatment groups with 
sample sizes equal to 40, 60, and 80 are 89.5%, 94.5%, and 96.5%, respectively. As an example, 
in a fixed design, with the placebo and LY3471851 treatment groups each having 80 participants, 
a 17% or larger difference between the groups can be detected with 90% power and assuming a 
5% placebo effect. 
 
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6. 
Supporting Documentation 
6.1. 
Appendix 1: Demographic and Baseline Characteristics 
The patient’s year of birth, sex, weight, height, smoking habits, previous biologic treatment, and 
other demographic characteristics are collected at the screening visit. Age and body mass index 
will be calculated.  
Only the year of birth is collected at screening. For the purpose of age calculation, the month and 
day of birth will be imputed as July 01, of the year of birth. Age is computed as follows; 
                             Age= (Informed Consent Date –Date of Birth +1)/365.25.  
Demographic and baseline characteristics (including age, gender, race, and ethnicity) will be 
summarized for each treatment group.  
Certain characteristics, that are collected at baseline or after baseline but not summarized in the 
demographic summary, will be reported as a listing. 
No inferential analysis for the comparability of baseline covariates across treatment groups will 
be performed. 
6.2. 
Appendix 2: Preexisting Conditions 
Preexisting condition is defined the condition/event recorded on the Preexisting Conditions and 
Medical History electronic case report form (eCRF) page with a start date prior to the date of 
informed consent, and no end date (that is, the event is ongoing) or an end date on or after the 
date of informed consent. In addition, the AEs occurring prior to first dose are also included. 
Notice if a preexisting condition worsens in severity on or after the date of informed consent, it 
will be recorded as an AE on the AE eCRF page with the date of worsening as the start date. The 
number and percentage of patients with preexisting conditions will be summarized by treatment 
group using the MedDRA Preferred Term (PT) nested within System Organ Class (SOC). 
Summaries will be performed for the ITT population. 
6.3. 
Appendix 3: Treatment Compliance 
Study treatment administration and compliance will be listed for all entered patients. The number 
and percentage of patients who are treatment compliant by week (that is, at each injection time 
point) will be summarized by treatment group for each treatment period. 
No patient will be excluded from the ITT population as a consequence of significant 
noncompliance.  
Participants who are noncompliant with treatment will be listed by treatment group. 
No analyses are planned to assess treatment compliance. 
6.4. 
Appendix 4: Prior and Concomitant Therapy 
Prior and concomitant medications will be summarized by treatment group and will be classified 
into anatomical therapeutic chemical (ATC) drug classes using the latest version of the World 
Health Organization (WHO) drug dictionary. Medication start and stop dates will be compared to 
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the date of first dose of treatment in each treatment period to allow medications to be classified 
as Concomitant for each treatment period. 
Prior medications are those medications that start and stop prior to the date of first dose of study 
treatment. Concomitant medications are those medications that start before, on or after the first 
day of study treatment of the defined treatment period and continue into the treatment period.  
6.5. 
Appendix 5: Clinical Trial Registry Analyses 
Additional analyses will be performed for the purpose of fulfilling the Clinical Trial Registry 
(CTR) requirements.   
Analyses provided for the CTR requirements include the following: 
Summary of adverse events, provided as a dataset which will be converted to an XML file.   
Both Serious Adverse Events and ‘Other’ Adverse Events are summarized: by treatment 
group, by MedDRA preferred term. 
 An adverse event is considered ‘Serious’ whether or not it is a treatment emergent 
adverse event (TEAE). 
 An adverse event is considered in the ‘Other’ category if it is both a TEAE and is not 
serious.  For each Serious AE and ‘Other’ AE, for each term and treatment group, the 
following are provided: 
o the number of participants at risk of an event 
o the number of participants who experienced each event term 
o the number of events experienced. 
 Consistent with www.ClinicalTrials.gov requirements, ‘Other’ AEs that occur in fewer 
than 5% of patients/subjects in every treatment group may not be included if a 5% 
threshold is chosen (5% is the minimum threshold). 
AE reporting is consistent with other document disclosures for example, the CSR, manuscripts, 
and so forth. 
6.6. 
Appendix 6: Daily Diary Calculations 
Weekly summary measures of daily diary data will be created for each patient. The 7-day period 
associated with each week will be defined using a visit centric approach. The table below 
displays the interval for each week: 
Week (Visit) 
Start Daya  
End Daya 
Baseline 
Week 0 Visit Date – 7  
Week 0 Visit Date – 1  
Week 1 (V3) 
Max(Week 0 Visit Date, Week 1 Visit Date – 7) 
Week 1 Visit Date – 1 
Week 2 (V4) 
Max(Week 1 Visit Date , Week 2 Visit Date – 7) 
Week 2 Visit Date – 1  
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Week 3 
Max (Week 2 Visit Date, Week 4 Visit Date – 14) 
Week 4 Visit Date – 8 
Week 4 (V5) 
Max (Week 2 Visit Date, Week 4 Visit Date – 7) 
Week 4 Visit Date – 1 
Week 5 
Max (Week 4 Visit Date, Week 6 Visit Date – 14) 
Week 6 Visit Date – 8 
Week 6 (V6) 
Max (Week 4 Visit Date, Week 6 Visit Date – 7) 
Week 6 Visit Date – 1 
Week 7 
Max (Week 6 Visit Date, Week 8 Visit Date – 14) 
Week 8 Visit Date – 8 
Week 8 (V7) 
Max (Week 6 Visit Date, Week 8 Visit Date – 7) 
Week 8 Visit Date – 1 
Week 9 
Max (Week 8 Visit Date, Week 10 Visit Date – 14) 
Week 10 Visit Date – 8 
Week 10 (V8) 
Max (Week 8 Visit Date, Week 10 Visit Date – 7) 
Week 10 Visit Date – 1 
Week 11 
Max (Week 10 Visit Date, Week 12 Visit Date – 14) 
Week 12 Visit Date – 8 
Week 12 (V9) 
Max (Week 10 Visit Date, Week 12 Visit Date – 7) 
Week 12 Visit Date – 1 
Week 13 
Max (Week 12 Visit Date, Week 14 Visit Date – 14) 
Week 14 Visit Date – 8 
Week 14 (V10) 
Max (Week 12 Visit Date, Week 14 Visit Date – 7) 
Week 14 Visit Date – 1 
Week 15 
Max (Week 14 Visit Date, Week 16 Visit Date – 14) 
Week 16 Visit Date – 8 
Week 16 (V11) 
Max (Week 14 Visit Date, Week 16 Visit Date – 7) 
Week 16 Visit Date – 1 
Week 17 
Max (Week 16 Visit Date, Week 18 Visit Date – 14) 
Week 18 Visit Date – 8 
Week 18 (V12) 
Max (Week 16 Visit Date, Week 18 Visit Date – 7) 
Week 18 Visit Date – 1 
Week 19 
Max (Week 18 Visit Date, Week 20 Visit Date – 14) 
Week 20 Visit Date – 8 
Week 20 (V13) 
Max (Week 18 Visit Date, Week 20 Visit Date – 7) 
Week 20 Visit Date – 1 
Week 21 
Max (Week 20 Visit Date, Week 22 Visit Date – 14) 
Week 22 Visit Date – 8 
Week 22 (V14) 
Max (Week 20 Visit Date, Week 22 Visit Date – 7) 
Week 22 Visit Date – 1 
Week 23 
Max (Week 22 Visit Date, Week 24 Visit Date – 14) 
Week 24 Visit Date – 8 
Week 24 (V15) 
Max (Week 22 Visit Date, Week 24 Visit Date – 7) 
Week 24 Visit Date – 1 
Week 25 
Max (Week 24 Visit Date, Week 26 Visit Date – 14) 
Week 26 Visit Date – 8 
Week 26 (V16) 
Max (Week 24 Visit Date, Week 26 Visit Date – 7) 
Week 26 Visit Date – 1 
Week 27 
Max(Week 26 Visit Date, Week 28 Visit Date – 14) 
Week 28 Visit Date – 1 
Week 28 (V17) 
Max(Week 26 Visit Date , Week 28 Visit Date – 7) 
Week 28 Visit Date – 1  
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Week 29 
Max (Week 28 Visit Date, Week 30 Visit Date – 14) 
Week 30 Visit Date – 8 
Week 30 (V18) 
Max (Week 28 Visit Date, Week 30 Visit Date – 7) 
Week 30 Visit Date – 1 
Week 31 
Max (Week 30 Visit Date, Week 32 Visit Date – 14) 
Week 32 Visit Date – 8 
Week 32 (V19) 
Max (Week 30 Visit Date, Week 32 Visit Date – 7) 
Week 32 Visit Date – 1 
Week 33 
Max (Week 32 Visit Date, Week 34 Visit Date – 14) 
Week 34 Visit Date – 8 
Week 34 (V20) 
Max (Week 32 Visit Date, Week 34 Visit Date – 7) 
Week 34 Visit Date – 1 
Week 35 
Max (Week 34 Visit Date, Week 36 Visit Date – 14) 
Week 36 Visit Date – 8 
Week 36 (V21) 
Max (Week 34 Visit Date, Week 36 Visit Date – 7) 
Week 36 Visit Date – 1 
Week 37 
Max (Week 36 Visit Date, Week 38 Visit Date – 14) 
Week 38 Visit Date – 8 
Week 38 (V22) 
Max (Week 36 Visit Date, Week 38 Visit Date – 7) 
Week 38 Visit Date – 1 
Week 39 
Max (Week 38 Visit Date, Week 40 Visit Date – 14) 
Week 40 Visit Date – 8 
Week 40 (V23) 
Max (Week 38 Visit Date, Week 40 Visit Date – 7) 
Week 40 Visit Date – 1 
Week 41 
Max (Week 40 Visit Date, Week 42 Visit Date – 14) 
Week 42 Visit Date – 8 
Week 42 (V24) 
Max (Week 40 Visit Date, Week 42 Visit Date – 7) 
Week 42 Visit Date – 1 
Week 43 
Max (Week 42 Visit Date, Week 44 Visit Date – 14) 
Week 44 Visit Date – 8 
Week 44 (V25) 
Max (Week 42 Visit Date, Week 44 Visit Date – 7) 
Week 44 Visit Date – 1 
Week 45 
Max (Week 44 Visit Date, Week 46 Visit Date – 14) 
Week 46 Visit Date – 8 
Week 46 (V26) 
Max (Week 44 Visit Date, Week 46 Visit Date – 7) 
Week 46 Visit Date – 1 
Week 47 
Max (Week 46 Visit Date, Week 48 Visit Date – 14) 
Week 48 Visit Date – 8 
Week 48 (V27) 
Max (Week 46 Visit Date, Week 48 Visit Date – 7) 
Week 48 Visit Date – 1 
Week 49 
Max (Week 48 Visit Date, Week 50 Visit Date – 14) 
Week 50 Visit Date – 8 
Week 50 (V28) 
Max (Week 48 Visit Date, Week 50 Visit Date – 7) 
Week 50 Visit Date – 1 
Week 51 
Max (Week 50 Visit Date, Week 52 Visit Date – 14) 
Week 52 Visit Date – 8 
Week 52 (V29) 
Max (Week 50 Visit Date, Week 52 Visit Date – 7) 
Week 52 Visit Date – 1 
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Abbreviations:  V = Visit. 
a 
If End Day < Start Day, do not assign specified visit week. Visit date will be calculated by selecting the first date 
from the following list (i.e., first in list order): (1) date of earliest bowel preparation if bowel preparation date is 
available, (2) date of endoscopy if endoscopy was performed, (3) date of treatment if treatment was given, (4) 
office visit date if available, or (5) imputed date of visit center of the protocol-defined window for that visit. The 
screening endoscopy is assumed to be associated with the Week 0 visit.  
For the Mayo SF and RB subscores, the most recent 3 nonmissing days of the 7-day period in the 
table above will be averaged and rounded to the nearest integer to calculate the weekly score for 
each patient. Patients with less than 3 measurements in the 7 day period will be considered 
missing. 
For the Bristol Stool Scale the worst (i.e. maximum) of the available measures during the 7 
period in the table above will be used to calculate a weekly score for each patient. If fewer than 4 
days are available (i.e., not missing), the patient will be considered to be missing data for that 
week. 
For all other daily diary measures, all available days of the 7 days will be averaged and rounded 
to the nearest integer to calculate the weekly score for each patient. If fewer than 4 days are 
available (i.e., not missing), the patient will be considered to be missing data for that week. 
If multiple diary assessments on a single day are present, use the earliest nonmissing assessment. 
Data from the following days will be considered missing: (i) days when patients receive bowel 
preparation, (ii) the day of an endoscopy, and (iii) two days after an endoscopy. 
If the baseline assessment is missing per the above rules, the first available postbaseline 
assessment starting with Week 1 will be used to impute the baseline so that the patient can be 
included in the analysis. 
6.7. 
Appendix 7: Execution for Bayesian Model Averaging 
6.7.1. 
R DREAMER Package to Execute BMA 
BMA will be executed using the R package DREAMER: Dose REsponse bAyesian Model 
averaging.  DREAMER package and supporting documentation may be found at GitHub - rich-
payne/dreamer and on CRAN. 
6.7.2. 
BMA Components, Priors, and Weights 
E-max, quadratic, log-quadratic, linear, and log-linear dose response models are the prespecified 
component to the BMA model that will be used to analyze the KFAH dose response and are 
described in the DREAMER supporting documentation.  BMA components and weights are 
summarized in Error! Reference source not found. The priors for each parameter are normal 
distributions, except 𝑏4 in the Sigmoidal EMAX model, which is truncated normal (to be 
positive). A logistic link function will be used for each model. 
Table KFAH.6. 
Prespecified Dose Response Models with Prior 
Component 
Weight 
Model 
Parameter 
mu 
sigma 
Sigmoidal EMAX 
1/6 
𝑓(𝑑) = 𝑏1 +
(𝑏2 −𝑏1)𝑑𝑏4
exp(𝑏3𝑏4) + 𝑑𝑏4 
b1 
-2 
2 
 
 
b2 
0 
4 
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b3 
log(
 
log(600) 
 
 
b4 
1 
2 
Hyperbolic EMAX 
1/6 
𝑓(𝑑) = 𝑏1 + (𝑏2 −𝑏1)𝑑
exp(𝑏3) + 𝑑 
b1 
-2 
2 
 
 
b2 
0 
4 
 
 
b3 
log(
 
log(600) 
Quadratic 
1/6 
𝑓(𝑑) = 𝑏1 + 𝑏2𝑑+ 𝑏3𝑑2 
b1 
-2 
2 
 
 
b2 
0 
2 
 
 
b3 
0 
2 
Log-Quadratic 
1/6 
𝑓(𝑑) = 𝑏1 + 𝑏2 log(𝑑+ 1)
+ 𝑏3 log(𝑑+ 1)2 
b1 
-2 
2 
 
 
b2 
0 
1 
 
 
b3 
0 
1 
Linear 
1/6 
𝑓(𝑑) = 𝑏1 + 𝑏2𝑑 
b1 
-2 
2 
 
 
b2 
0 
2 
Log-Linear 
1/6 
𝑓(𝑑) = 𝑏1 + 𝑏2 log(𝑑+ 1) 
b1 
-2 
2 
 
 
b2 
0 
1 
6.8. 
Appendix 8: List of MedDRA Preferred Terms for Potential 
Opportunistic Infections (POI) 
Category 
Potential 
Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Mycobacterial/ 
Actino 
Nocardiosis (II) 
Nocardia sepsis  
10064952 
Narrow 
Nocardiosis 
10029444 
Nocardia test positive 
10070131 
Broad 
Mycobacterial/ 
Actino 
Nontuberculous 
mycobacterium 
disease (II) 
Atypical mycobacterial 
infection  
10061663 
Narrow 
Atypical mycobacterial 
lower respiratory tract 
infection  
10075026 
Atypical mycobacterial 
lymphadenitis  
10003755 
Atypical mycobacterium 
pericarditis 
10055036 
Atypical mycobacterial 
pneumonia  
10071075 
Borderline leprosy 
10006029 
Bovine tuberculosis 
10006049 
Indeterminate leprosy  
10021700 
Leprosy 
10024229 
Lepromatous leprosy 
10024227 
Mycobacterial infection  
10062207 
Mycobacterial 
peritonitis  
10073514 
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Category 
Potential 
Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Mycobacterium 
abscessus infection 
10064789 
Mycobacterium avium 
complex immune 
restoration disease  
10058449 
 
Mycobacterium avium 
complex infection  
10058806 
Mycobacterium 
chelonae infection 
10071401 
Mycobacterium 
fortuitum infection  
10049659 
Mycobacterium kansasii 
infection 
10028447 
Mycobacterium 
marinum infection  
10028452 
Mycobacterium ulcerans 
infection  
10066289 
Superinfection 
mycobacterial 
10075381 
Tuberculoid leprosy 
10044729 
Type 1 lepra reaction 
10070516 
Type 2 lepra reaction 
10070517 
Atypical mycobacterium 
test positive  
10070326 
Broad 
Mycobacterial disease 
carrier 
10075025 
Mycobacterium leprae 
test positive 
10070324 
Mycobacterium test  
10070407 
Mycobacterium test 
positive 
10070323 
Ureaplasmal 
ulvovaginitis 
10081280 
Mycobacterial/ 
Actino 
Tuberculosis (I) 
Adrenal gland 
tuberculosis  
10001358 
Narrow 
Bone tuberculosis  
10056377 
Choroid tubercles 
10008779 
Congenital tuberculosis 
10010657 
Conjunctivitis 
tuberculous 
10010754 
Cutaneous tuberculosis  
10011684 
Disseminated Bacillus  
Calmette-Guerin 
infection  
10076666 
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Category 
Potential 
Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Disseminated 
tuberculosis 
10013453 
Ear tuberculosis  
10014027 
Epididymitis 
tuberculous  
10015004 
Extrapulmonary 
tuberculosis  
10064445 
Female genital tract 
tuberculosis  
10061150 
Immune reconstitution 
inflammatory syndrome 
associated tuberculosis 
10072797 
 
Intestinal tuberculosis  
10075268 
Joint tuberculosis  
10056367 
Lupus vulgaris  
10025143 
Lymph node 
tuberculosis  
10025183 
Male genital tract 
tuberculosis  
10061234 
Meningitis tuberculous  
10027259 
Oesophageal 
tuberculosis  
10030200 
Oral tuberculosis  
10076879 
Pericarditis tuberculous  
10055069 
Peritoneal tuberculosis  
10053583 
Prostatitis tuberculous  
10064743 
Pulmonary tuberculoma  
10066927 
Pulmonary tuberculosis  
10037440 
Renal tuberculosis  
10038534 
Salpingitis tuberculous  
10039463 
Silicotuberculosis  
10068876 
Spleen tuberculosis  
10041640 
Thyroid tuberculosis  
10043774 
Tuberculoma of central 
nervous system 
10052883 
Tuberculosis 
10044755 
Tuberculosis bladder  
10044758 
Tuberculosis 
gastrointestinal  
10061390 
Tuberculosis liver  
10058120 
Tuberculosis of central 
nervous system  
10061391 
Tuberculosis of eye  
10044819 
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Category 
Potential 
Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Tuberculosis of 
genitourinary system  
10044828 
Tuberculosis of 
intrathoracic lymph 
nodes  
10044846 
Tuberculosis of 
peripheral lymph nodes  
10044965 
Tuberculosis ureter  
10045026 
Tuberculous abscess 
central nervous system  
10052884 
Tuberculous 
endometritis  
10071559 
Tuberculous laryngitis  
10045072 
Tuberculous pleurisy  
10045104 
Tuberculous 
tenosynovitis 
10059161 
Interferon gamma 
release assay 
10073542 
Broad 
Interferon gamma 
release assay positive 
10072866 
Mycobacterium 
tuberculosis complex 
test 
10070472 
Mycobacterium 
tuberculosis complex 
test positive 
10070325 
Tuberculid  
10044725 
Tuberculin test  
10044726 
Tuberculin test false 
negative  
10074840 
Tuberculin test positive 
10044728 
Bacteria 
 
Bartonellosis 
(disseminated disease 
only) (V) 
Bacillary angiomatosis 
10003971 
Narrow 
Trench fever 
10044582 
Bartonella test  
10075209 
Broad 
Bartonella test positive  
10070157 
Bartonellosis 
10004145 
Cat scratch disease 
10007729 
Peliosis hepatis  
10034229 
Splenic peliosis 
10068851 
Campylobacteriosis 
(invasive disease 
only) (V) 
Campylobacter sepsis  
10070681 
Narrow 
Campylobacter colitis 
10076769 
Broad 
Campylobacter 
gastroenteritis  
10007048 
Campylobacter infection 
10051226 
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Category 
Potential 
Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Campylobacter test 
positive 
10070025 
Legionellosis (II) 
Legionella infection 
10061266 
Narrow 
Pneumonia legionella  
10035718 
Pontiac fever 
10054161 
Legionella test  
10070410 
Broad 
Legionella test positive 
10070092 
Bacteria 
 
Listeria 
monocytogenes 
(invasive disease 
only) (II) 
Listeria encephalitis  
10054116 
Narrow 
Listeria sepsis  
10063085 
Meningitis listeria 
10027248 
Listeria test  
10075707 
Broad 
Listeria test positive 
10070094 
Listeriosis 
10024641 
Salmonellosis 
(invasive disease 
only) (II) 
Aortitis salmonella  
10074937 
Narrow 
Arthritis salmonella 
10003271 
Meningitis salmonella 
10027254 
Osteomyelitis 
salmonella 
10031262 
Paratyphoid fever 
10033971 
Pneumonia salmonella 
10035733 
Salmonella bacteraemia 
10058924 
Salmonella sepsis 
10058878 
Typhoid fever 
10045275 
Salmonella test positive  
10070127 
Broad 
 
Salmonellosis 
10039447 
Salmonella test 
10079854 
Bacteria 
Shigellosis (invasive 
disease only) (V) 
Shigella sepsis  
10074481 
Narrow 
Shigella infection  
10054178 
Broad 
Shigella test positive 
10070129 
Vibriosis (invasive 
disease due to V. 
vulnificus) (V) 
Gastroenteritis vibrio  
10017917 
Broad 
Vibrio test positive 
10070161 
None 
 
Narrow 
Infective Pneumonia 
SMQ 
 
Pneumonia 
acinetobacter 
10079866 
 
 
Narrow 
Pneumonia proteus 
10079867 
Pneumonia serratia 
10079868 
Fungal 
Aspergillosis 
(invasive disease 
only) (II) 
Aspergillosis oral  
10003489 
 
Cerebral aspergillosis  
10051597 
Meningitis aspergillus  
10073245 
Oro-pharyngeal 
aspergillosis 
10053029 
Aspergillus infection  
10074171 
 
Aspergillus test  
10070450 
Aspergillus test positive 
10070448 
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Category 
Potential 
Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Bronchopulmonary 
aspergillosis 
10006473 
Sinusitis aspergillus 
10051016 
Blastomycosis (IV) 
 
Blastomycosis  
10005098 
Narrow 
Epididymitis 
blastomyces  
10015001 
Osteomyelitis 
blastomyces  
10031255 
Pneumonia blastomyces 
10035671 
None 
 
Broad 
Candidiasis (invasive 
disease, or oral not 
limited to the tongue) 
(II) 
Candida 
endophthalmitis 
10059449 
Narrow 
Candida osteomyelitis 
10064699 
Candida pneumonia  
10053158 
Candida retinitis  
10068612 
Candida sepsis  
10053166 
Candida urethritis 
10081262 
Candidiasis of trachea  
10064459 
Cerebral candidiasis  
10078126 
Endocarditis candida 
10014669 
Gastrointestinal 
candidiasis  
10017938 
Hepatic candidiasis 
10049653 
Hepatosplenic 
candidiasis 
10051590 
Meningitis candida  
10027205 
Oesophageal candidiasis  10030154 
Oral candidiasis  
10030963 
Oropharyngeal 
candidiasis  
10050346 
Peritoneal candidiasis 
10056562 
Splenic candidiasis  
10051725 
Systemic candida 
10042938 
Bladder candidiasis  
10058523 
Broad 
Candida infection  
10074170 
Candida test  
10070453 
Candida test positive  
10070451 
Mucocutaneous 
candidiasis1  
10028080 
Respiratory moniliasis 
10038705 
Coccidioidomycosis 
(II) 
Coccidioides 
encephalitis  
10054214 
Narrow 
Coccidioidomycosis  
10009825 
Cutaneous 
coccidioidomycosis  
10068747 
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Category 
Potential 
Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Meningitis coccidioides 
10027207 
None 
 
Broad 
Cryptococcosis (II) 
Cryptococcal cutaneous 
infection  
10054216 
Narrow 
Cryptococcal fungaemia  10067112 
Cryptococcosis  
10011490 
Disseminated 
cryptococcosis  
10013439 
Gastroenteritis 
cryptococcal  
10011485 
Meningitis cryptococcal  
10027209 
Neurocryptococcosis  
10068368 
Pneumonia cryptococcal 
10067565 
Cryptococcus test  
10070456 
Broad 
 
Cryptococcus test 
positive 
10070455 
Histoplasmosis (II) 
Acute pulmonary 
histoplasmosis  
10001027 
Narrow 
Chronic pulmonary 
histoplasmosis  
10009115 
Endocarditis 
histoplasma  
10014676 
Histoplasmosis 
10020141 
Histoplasmosis 
cutaneous  
10049142 
Histoplasmosis 
disseminated 
10020144 
Meningitis histoplasma 
10027243 
Pericarditis histoplasma 
10034489 
Retinitis histoplasma 
10038912 
Presumed ocular 
histoplasmosis 
syndrome 
10063664 
Broad 
Microsporidiosis (IV) 
Microsporidia infection  
10053982 
Narrow 
None 
 
Broad 
Other invasive fungi:  
Mucormycosis 
(=zygomycosis) 
[Rhizopus, Mucor, 
and Lichtheimia], 
Scedosporum/ 
Pseudallescheria 
boydii, Fusarium (II) 
Allescheriosis  
10001754 
Narrow 
Fusarium infection  
10051919 
Mucormycosis  
10028098 
Scedosporium infection  
10059045 
Pseudallescheria 
infection  
10061919 
Pseudallescheria sepsis 
10058973 
See “Non-specific 
terms” below  
 
Broad 
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Category 
Potential 
Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Paracoccidioides 
infections (V) 
Paracoccidioides 
infection  
10061906 
Narrow 
None 
 
Broad 
Penicillium marneffei 
(V) 
Penicillium infection 
10078580 
Narrow 
None 
 
Broad 
Pneumocystis 
jirovecii (II) 
 
Pneumocystis jirovecii 
infection 
10073756 
Narrow 
 
Pneumocystis jirovecii 
pneumonia 
10073755 
Blood beta-D-glucan  
10068725 
Broad 
Blood beta-D-glucan 
abnormal  
10051795 
Blood beta-D-glucan 
increased 
10051793 
Gomori methenamine 
silver stain  
10075549 
Carbon monoxide 
diffusing capacity 
decreased  
10065906 
Carbon monoxide 
diffusing capacity 
10071738 
Pneumocystis test 
positive 
10070454 
Sporothrix schenckii 
(V) 
Cutaneous 
sporotrichosis  
10011676 
Narrow 
Sporotrichosis 
10041736 
None 
 
Broad 
Viral 
Cytomegalovirus 
disease (V) 
Cytomegalovirus 
chorioretinitis  
10048843 
Narrow 
Cytomegalovirus colitis  
10048983 
Cytomegalovirus 
duodenitis 
10049014 
Cytomegalovirus 
enteritis  
10049074 
Cytomegalovirus 
enterocolitis  
10049015 
Cytomegalovirus 
gastritis  
10049016 
Cytomegalovirus 
gastroenteritis  
10051349 
Cytomegalovirus 
gastrointestinal infection 
10052817 
Cytomegalovirus 
gastrointestinal ulcer 
10075619 
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Category 
Potential 
Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Cytomegalovirus 
hepatitis  
10011830 
Cytomegalovirus 
infection  
10011831 
Cytomegalovirus 
mononucleosis  
10011834 
Cytomegalovirus 
mucocutaneous ulcer  
10065036 
Cytomegalovirus 
myelomeningoradiculitis  
10065621 
Cytomegalovirus 
myocarditis 
10056261 
Cytomegalovirus 
nephritis 
10079095 
Cytomegalovirus 
oesophagitis 
10049018 
Cytomegalovirus 
pancreatitis  
10049566 
Cytomegalovirus 
pericarditis  
10056721 
Cytomegalovirus 
syndrome 
10056262 
Cytomegalovirus 
urinary tract infection  
10051350 
Cytomegalovirus 
viraemia  
10058854 
Disseminated 
cytomegaloviral 
infection 
10049075 
Encephalitis 
cytomegalovirus  
10014586 
Pneumonia 
cytomegaloviral 
10035676 
Cytomegalovirus test  
10061806 
Broad 
Cytomegalovirus test 
positive 
10051620 
HBV reactivation 
(IV) 
None 
 
Narrow 
Asymptomatic viral 
hepatitis  
10063838 
Broad 
Chronic hepatitis B  
10008910 
HBV-DNA polymerase 
increased 
10058937 
Hepatitis B 
10019731 
Hepatitis B antigen 
10063414 
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Category 
Potential 
Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Hepatitis B antigen 
positive  
10063411 
Hepatitis B core antigen  
10051160 
Hepatitis B core antigen 
positive 
10052328 
Hepatitis B DNA assay  
10060027 
Hepatitis B DNA assay 
positive  
10060047 
Hepatitis B DNA 
increased 
10068379 
Hepatitis B e antigen  
10050914 
Hepatitis B e antigen 
positive  
10052329 
Hepatitis B reactivation 
10058827 
Hepatitis B surface 
antigen  
10050529 
Hepatitis B surface 
antigen positive 
10019742 
Hepatitis B virus test  
10068415 
Hepatitis B virus test 
positive  
10070217 
Hepatitis A 
10019780 
Hepatitis post 
transfusion 
10019791 
Hepatitis viral  
10019799 
Withdrawal hepatitis 
10071220 
Viral 
HCV progression (V) 
None 
 
Narrow 
Chronic hepatitis C  
10008912 
Broad 
Hepatitis C 
10019744 
Hepatitis C RNA  
10019748 
Hepatitis C RNA 
fluctuation  
10068727 
Hepatitis C RNA 
increased  
10068377 
Hepatitis C RNA 
positive  
10019750 
Hepatitis C virus test  
10068416 
Hepatitis C virus test 
positive 
10070218 
Herpes simplex (IV) 
 
 
 
 
Colitis herpes  
10051782 
Narrow 
 
 
 
Eczema herpeticum  
10014197 
Gastritis herpes  
10051784 
Herpes oesophagitis  
10052330 
Herpes sepsis 
10058876 
Herpes simplex colitis  
10074239 
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Category 
Potential 
Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Herpes simplex 
encephalitis 
10019953 
Herpes simplex gastritis  
10074240 
Herpes simplex hepatitis  10067389 
Herpes simplex 
meningitis  
10019956 
Herpes simplex 
meningoencephalitis  
10074247 
Herpes simplex 
meningomyelitis  
10074250 
Herpes simplex 
necrotising retinopathy 
10074252 
Herpes simplex 
oesophagitis  
10074242 
Herpes simplex 
pneumonia 
10065046 
Herpes simplex sepsis   
10074246 
Herpes simplex visceral 
10019963 
Meningitis herpes  
10027242 
Meningoencephalitis 
herpetic 
10027285 
Meningomyelitis herpes  
10074249 
Pneumonia herpes viral 
10035703 
Genital herpes simplex 
10073931 
Herpes dermatitis  
10062639 
Herpes pharyngitis  
10066888 
Herpes simplex otitis 
externa  
10019959 
Herpes simplex 
pharyngitis  
10074244 
Ophthalmic herpes 
simplex  
10073938 
Proctitis herpes 
10036780 
Kaposi's varicelliform 
eruption 
10051891 
Herpes simplex test 
positive 
10077969 
Broad 
 
 
 
 
Herpes simplex 
10019948 
Herpes virus infection  
10019973 
Nasal herpes  
10074936 
Oral herpes  
10067152 
Genital herpes  
10018150 
Herpes zoster (any 
form) (II) 
 
Disseminated varicella 
zoster vaccine virus 
infection  
10076667 
 
Narrow 
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Category 
Potential 
Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Encephalitis post 
varicella  
10014603 
Genital herpes zoster  
10072210 
Herpes zoster 
10019974 
Herpes zoster cutaneous 
disseminated  
10074297 
Herpes zoster 
disseminated 
10065038 
Herpes zoster infection 
neurological  
10061208 
Herpes zoster meningitis 
10074259 
Herpes zoster 
meningoencephalitis 
10074248 
Herpes zoster 
meningomyelitis  
10074251 
Herpes zoster 
meningoradiculitis 
10079327 
Herpes zosternecrotising 
retinopathy  
10074253 
Herpes zoster oticus 
10063491 
Herpes zoster 
pharyngitis  
10074245 
Necrotising herpetic 
retinopathy 
10065119 
Ophthalmic herpes 
zoster 
10030865 
Varicella 
10046980 
Varicella keratitis  
10077496 
Varicella post vaccine  
10063522 
Varicella zoster gastritis 
10074241 
Varicella zoster 
oesophagitis  
10074243 
Varicella zoster 
pneumonia 
10074254 
Varicella zoster virus 
infection 
10075611 
Herpes ophthalmic  
10062004 
Varicella virus test  
10070444 
Broad 
Varicella virus test 
positive 
10070214 
BK virus infection 
10055181 
Narrow 
 
Human polyomavirus 
infection  
10057366 
JC virus granule cell 
neuronopathy  
10074361 
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Category 
Potential 
Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Human Polyomavirus 
infection including 
BK virus disease and 
PVAN (V), and 
Progressive 
Multifocal 
Leukoencephalopathy 
(IV) 
JC virus infection 
10023163 
Polyomavirus-associated 
nephropathy  
10065381 
Progressive multifocal 
leukoencephalopathy 
10036807 
JC virus test  
10068794 
Broad 
 
Polyomavirus test  
10075038 
Polyomavirus test 
positive 
10070342 
Post-transplant 
lymphoproliferative 
disorder (EBV) (V) 
Epstein-Barr virus 
associated 
lymphoproliferative 
disorder  
10068349 
Narrow 
Post transplant 
lymphoproliferative 
disorder 
10051358 
Epstein-Barr viraemia 
10065110 
Broad 
Epstein-Barr virus 
associated lymphoma 
10071441 
Epstein-Barr virus 
infection 
10015108 
Lymphoproliferative 
disorder 
10061232 
Lymphoproliferative 
disorder in remission  
10061233 
Oral hairy leukoplakia 
10030979 
Parasites 
 
Trypanosoma cruzi 
infection (Chagas’ 
Disease) 
(disseminated disease 
only) (V) 
None 
 
Narrow 
American 
trypanosomiasis  
10001935 
Broad 
Trypanosomiasis 
10044707 
Meningitis 
trypanosomal 
10027258 
Cryptosporidium 
species (chronic 
disease only) (IV) 
Biliary tract infection 
cryptosporidial  
10067319 
Narrow 
Cryptosporidiosis 
infection  
10011502 
Broad 
Gastroenteritis 
cryptosporidial 
10017899 
Leishmaniasis 
(Visceral only) (IV) 
Visceral leishmaniasis  
10047505 
Narrow 
Leishmaniasis 
10024198 
Broad 
Stronglyoides 
(hyperinfection 
syndrome and 
disseminated forms 
only) (IV) 
None  
 
Narrow 
Strongyloidiasis 
10042254 
Broad 
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Category 
Potential 
Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Toxoplasmosis (IV) 
Cerebral toxoplasmosis 
10057854 
Narrow 
Eye infection 
toxoplasmal  
10015939 
Hepatitis toxoplasmal  
10019798 
Meningitis toxoplasmal  
10048848 
Myocarditis toxoplasmal  10028617 
Pneumonia toxoplasmal 
10067566 
Toxoplasma serology  
10050941 
Broad 
Toxoplasmosis 
10044272 
Non-specific 
terms 
 
Non-specific terms  
 
 
None 
 
Narrow 
 
 
Delftia acidovorans 
infection 
10081339 
Sphingomonas 
paucimobilis 
bacteraemia 
10081563 
Central nervous system 
immune reconstitution 
inflammatory response 
10080100 
Broad 
Abscess fungal  
10000269 
Alternaria infection  
10054207 
Arthritis fungal  
10060966 
Biliary tract infection 
fungal  
10065203 
Central nervous system 
fungal infection 
10072805 
Cerebral fungal 
infection  
10049657 
Encephalitis fungal  
10065170 
Erythema induratum  
10015213 
Eye infection fungal  
10015933 
Fungaemia 
10017523 
Fungal abscess central 
nervous system  
10017524 
Fungal endocarditis  
10017529 
Fungal labyrinthitis  
10065174 
Fungal oesophagitis  
10049656 
Fungal peritonitis  
10061138 
Fungal pharyngitis  
10076516 
Fungal retinitis  
10068613 
Fungal sepsis 
10058872 
Fungal urethritis 
10081163 
Hepatic infection fungal  
10065217 
Meningitis fungal  
10027236 
Mycotic 
endophthalmitis  
10063202 
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Category 
Potential 
Opportunistic 
Infection 
Preferred Term 
(MedDRA Version 
22.1) 
Preferred Term 
Code 
Lilly Defined 
Classification 
Myocarditis mycotic  
10059026 
Oral fungal infection  
10061324 
Oropharyngitis fungal  
10061891 
Osteomyelitis fungal  
10065239 
Otitis media fungal  
10065175 
Pancreatitis fungal  
10065190 
Pericarditis fungal  
10065220 
Phaehyphomycosis 
10034799 
Pneumonia fungal  
10061354 
Pulmonary mycosis  
10037422 
Pulmonary 
trichosporonosis  
10068184 
Sinusitis fungal  
10058678 
Splenic infection fungal 
10065194 
Systemic mycosis 
10052366 
Pneumonia 
Infective Pneumonia 
SMQ 
All PTs 
20000231 
Narrow 
Abbreviations:  DNA = deoxyribonucleic acid; EBV= Epstein-Barr virus; HBV = hepatitis B virus; MedDRA = 
Medical Dictionary for Regulatory Activities; PT = preferred term; PVAN = Polyomavirus-associated 
nephropathy; SMQ = standardized MedDRA query. 
6.9. 
Appendix 9: List of MedDRA Preferred Terms for Elevated or 
Increased Lipids from the Dyslipidemia SMQ (SMQ20000026) 
Preferred Term (MedDRA Version 20.0) 
Preferred Term Code 
Apolipoprotein B/Apolipoprotein A-1 ratio increased 
10065516 
Autoimmune hyperlipidaemia 
10071577 
Blood cholesterol abnormal 
10005423 
Blood cholesterol increased 
10005425 
Blood triglycerides abnormal 
10005837 
Blood triglycerides increased 
10005839 
Diabetic dyslipidaemia 
10070901 
Dyslipidaemia 
10058108 
Familial hypertriglyceridaemia 
10059183 
Fat overload syndrome 
10074028 
High density lipoprotein abnormal 
10020051 
High density lipoprotein decreased 
10020060 
High density lipoprotein increased 
10020061 
Hypercholesterolaemia 
10020603 
Hyperlipidaemia 
10062060 
Hypertriglyceridaemia 
10020869 
Hypo HDL cholesterolaemia 
10068961 
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6.10. 
Appendix 10: List of Planned Laboratory Analytes with Reference 
Range Sources 
Laboratory  
Laboratory Analyte 
Reference  
Analysis Type 
Group/Order 
 
Range Name 
Central 
Tendency 
Outlier/Shift 
Analysis 
Hematology 
 
 
1 
Hemoglobin 
LCTPB 
Yes 
Yes 
2 
Hematocrit 
LCTPB 
Yes 
Yes 
3 
Erythrocyte Count  
LCTPB 
Yes 
Yes 
4 
Mean Cell Volume 
LCTPB 
Yes 
Yes 
5 
Mean Cell Hemoglobin 
LCTPB 
Yes 
Yes 
6 
MCHC 
LCTPB 
Yes 
Yes 
7 
Platelets 
LCTPB 
Yes 
Yes 
8 
Leukocyte Count  
LCTPB 
Yes 
Yes 
9 
Bands   
LCTPB 
Yes 
Yes 
10 
Neutrophils 
LCTPB 
Yes 
Yes 
11 
Lymphocytes 
LCTPB 
Yes 
Yes 
12 
Monocytes 
LCTPB 
Yes 
Yes 
13 
Eosinophils 
LCTPB 
Yes 
Yes 
14 
Basophils 
LCTPB 
Yes 
Yes 
Chemistry 
 
 
Intermediate density lipoprotein increased 
10064236 
LDL/HDL ratio increased 
10049030 
Lipid metabolism disorder 
10061227 
Lipids abnormal 
10024588 
Lipids increased 
10024592 
Lipoprotein (a) abnormal 
10054023 
Lipoprotein (a) increased 
10054009 
Low density lipoprotein abnormal 
10024901 
Low density lipoprotein increased 
10024910 
Non-high-density lipoprotein cholesterol increased 
10063967 
Remnant hyperlipidaemia 
10038316 
Total cholesterol/HDL ratio abnormal 
10058633 
Total cholesterol/HDL ratio increased 
10058630 
Type I hyperlipidaemia 
10060749 
Type II hyperlipidaemia 
10045254 
Type IIa hyperlipidaemia 
10045261 
Type IIb hyperlipidaemia 
10045263 
Type III hyperlipidaemia 
10060751 
Type IV hyperlipidaemia 
10060753 
Type V hyperlipidaemia 
10060755 
Very low density lipoprotein abnormal 
10047352 
Very low density lipoprotein increased 
10047361 
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Laboratory  
Laboratory Analyte 
Reference  
Analysis Type 
Group/Order 
 
Range Name 
Central 
Tendency 
Outlier/Shift 
Analysis 
1 
ALT/SGPT 
Labcorp 
Yes 
Yes 
2 
AST/SGOT 
Labcorp 
Yes 
Yes 
3 
Alkaline Phosphatase 
Labcorp 
Yes 
Yes 
4 
Total Bilirubin 
Labcorp 
Yes 
Yes 
5 
Direct Bilirubin 
Labcorp 
Yes 
Yes 
6 
Albumin 
LCTPB 
Yes 
Yes 
7 
Creatine Phosphokinase 
LCTPB 
Yes 
Yes 
8 
Creatinine 
Labcorp 
Yes 
Yes 
9 
Urea Nitrogen 
LCTPB 
Yes 
Yes 
11 
estimated GFR  
Labcorp 
Yes 
Yes 
12 
Creatinine Clearance 
Labcorp 
Yes 
Yes 
13 
Sodium 
LCTPB 
Yes 
Yes 
14 
Potassium 
LCTPB 
Yes 
Yes 
15 
Calcium 
LCTPB 
Yes 
Yes 
16 
Total Protein 
LCTPB 
Yes 
Yes 
17 
Fasting Glucose 
LCTPB 
Yes 
Yes 
18 
Glucose, Non-Fasting or Random 
LCTPB 
Yes 
Yes 
19 
Uric Acid 
LCTPB 
Yes 
Yes 
20 
Cholesterol 
LCTPB 
Yes 
Yes 
21 
Triglycerides 
LCTPB 
Yes 
Yes 
22 
LDL Cholesterol – Direct 
Labcorp 
Yes 
Yes 
23 
HDL Cholesterol – Direct 
Labcorp 
Yes 
Yes 
24 
LDL/HDL Ratio – Calculated 
None 
Yes 
No 
 
 
 
 
 
Immunoglobulins 
 
 
1 
Immunoglobulin A 
Labcorp 
Yes 
Yes 
2 
Immunoglobulin G 
Labcorp 
Yes 
Yes 
3 
Immunoglobulin M 
Labcorp 
Yes 
Yes 
Urinalysis 
 
 
1 
Specific Gravity 
LCTPB 
Yes 
Yes 
2 
pH 
LCTPB 
Yes 
Yes 
3 
UA-color 
None 
No 
Yes 
4 
UA-glucose 
None 
No 
Yes 
5 
UA-protein 
None 
No 
Yes 
6 
UA-bilirubin 
None 
No 
Yes 
7 
UA-urobilinogen 
None 
No 
Yes 
8 
UA-nitrites 
None 
No 
Yes 
9 
UA-leukoesterase 
None 
No 
Yes 
10 
UA-ketones 
None 
No 
Yes 
11 
UA-occult blood 
None 
No 
Yes 
Flow Cytometry 
 
 
1 
CD3+ T Cells – % 
Labcorp 
Yes 
Yes 
2 
CD3+ T Cells – Absolute 
Labcorp 
Yes 
Yes 
3 
CD3+CD4+ T cells (CD4) – % 
Labcorp 
Yes 
Yes 
4 
CD3+CD4+ T cells (CD4) – Absolute 
Labcorp 
Yes 
Yes 
5 
CD3+CD8+ T cells (CD8) – % 
Labcorp 
Yes 
Yes 
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Laboratory  
Laboratory Analyte 
Reference  
Analysis Type 
Group/Order 
 
Range Name 
Central 
Tendency 
Outlier/Shift 
Analysis 
6 
CD3+CD8+ T cells (CD8) – Absolute 
Labcorp 
Yes 
Yes 
7 
CD56+/CD16+ NK cells – % 
Labcorp 
Yes 
Yes 
8 
CD56+/CD16+ NK cells – Absolute 
Labcorp 
Yes 
Yes 
9 
CD19+ B cells – % 
Labcorp 
Yes 
Yes 
10 
CD19+ B cells – Absolute 
Labcorp 
Yes 
Yes 
11 
CD4+CXCR3+CCR6- Th1 cells - % 
None 
Yes 
No 
12 
CD4+CXCR3+CCR6- Th1 cells - 
Absolute 
None 
Yes 
No 
13 
CD4+CXCR3-CCR6+ Th17 cells - % 
None 
Yes 
No 
14 
CD4+CXCR3-CCR6+ Th17 cells - 
Absolute 
None 
Yes 
No 
15 
CD3+CD4+CD127-
/loCD25+FoxP3+ (CD4+) T 
regulatory cells - % 
None 
Yes 
No 
16 
CD3+CD4+CD127-
/loCD25+FoxP3+ (CD4+) T 
regulatory cells - Absolute 
None 
Yes 
No 
17 
CD3+CD4+CD127-/loCD25+ 
(CD4+) IL2-producing naïve and 
central memory Helper T cells - % 
None 
Yes 
No 
18 
CD3+CD4+CD127-/loCD25+ 
(CD4+) IL2-producing naïve and 
central memory Helper T cells - 
Absolute 
None 
Yes 
No 
19 
CD20+ B cells – % 
 None 
Yes 
No 
20 
CD20+ B cells – Absolute 
 None 
Yes 
No 
21 
CD19+CD27-IgD+ mature naïve B 
cells – % 
 None 
Yes 
No 
22 
CD19+CD27-IgD+ mature naïve B 
cells – Absolute 
 None 
Yes 
No 
23 
CD19+CD27+IgD- switched 
memory B cells – % 
 None 
Yes 
No 
24 
CD19+CD27+IgD- switched 
memory B – Absolute 
 None 
Yes 
No 
25 
CD19+CD27+IgD+ non-switched 
memory B cells – % 
 None 
Yes 
No 
26 
CD19+CD27+IgD+ non-switched 
memory B – Absolute 
 None 
Yes 
No 
27 
CD19+CD27-IgD- 
Immature/transitional B cells – % 
 None 
Yes 
No 
28 
CD19+CD27-IgD- 
Immature/transitional B – Absolute 
 None 
Yes 
No 
29 
CD4/CD8 Ratio – Calculated 
None 
Yes 
No 
-- 
CD4+CD45RA-CCR7- effector 
memory T cells  
None 
No 
No 
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Laboratory  
Laboratory Analyte 
Reference  
Analysis Type 
Group/Order 
 
Range Name 
Central 
Tendency 
Outlier/Shift 
Analysis 
-- 
CD4+CD45RA+CCR7- effector 
memory T cells  
None 
No 
No 
-- 
CD4+CD45RA+CCR7- naïve T 
cells  
None 
No 
No 
-- 
CD4+CD45RA-CCR7+ central 
memory T cells  
None 
No 
No 
 -- 
CD8+CD45RA+CCR7+ naïve T 
cells  
None 
No 
No 
-- 
CD8+CD45RA-CCR7+ central 
memory T cells  
None 
No 
No 
-- 
CD8+CD45RA-CCR7- effector 
memory T cells  
None 
No 
No 
 
CD8+CD45RA+CCR7- effector 
memory T cells  
None 
No 
No 
Abbreviations:  ALT/SGPT = alanine aminotransferase/serum glutamic pyruvic transaminase; AST/SGOT = 
aspartate aminotransferase/serum glutamic oxaloacetic transaminase; CD = cluster of differentiation; eGFR = 
estimated glomerular filtration rate; HDL = high-density lipoprotein; LCTPB = Lilly Large Clinical Trial 
Population Based; LDL = low-density lipoprotein; MCHC = mean corpuscular hemoglobin concentration; NK = 
natural killer; UA = urinalysis. 
 
 
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7. 
References 
Bretz F, Pinheiro JC, Branson M. Combining multiple comparisons and modeling techniques 
in dose-response studies. Biometrics. 2005;61(3):738-748. https://doi.org/ 10.1111/j.1541-
0420.2005.00344.x 
[FDA] Food and Drug Administration. E9(R1): statistical principles for clinical trials: 
addendum: estimands and sensitivity analyses in clinical trials: guidance for industry. Draft 
Guidance. Available at: 
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidance
s/UCM582738.pdf. Published 16 June 2017. Accessed 23 November 2019. 
[FDA] Food and Drug Administration. Qualification of the MCP-Mod Procedure. Available at: 
FDA Qualification of MCP-MOD Method. Application date 22 April 2015. 
Gould AL. BMA-Mod: A Bayesian model averaging strategy for determining dose-response 
relationships in the presence of model uncertainty. Biom J. 2019;61(5):1141-1159. 
https://doi.org/ 10.1002/bimj.201700211 
 
Approved on 18 Mar 2022 GMT


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