A Phase 2, Dose-finding, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of Efavaleukin Alfa Induction Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis
Phase: PHASE2
Conditions: Ulcerative Colitis
Sponsor: Amgen

Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
Date:  21 August 2024 
Page 1 of 131 
CONFIDENTIAL 
Title Page 
Protocol Title: 
A Phase 2, Dose-finding, Randomized, 
Double-blind, Placebo-controlled, Multicenter 
Study to Evaluate the Safety and Efficacy of 
Efavaleukin Alfa Induction Therapy in Subjects 
with Moderately to Severely Active Ulcerative 
Colitis 
Short Protocol Title: 
Safety and Efficacy of Efavaleukin Alfa in 
Subjects with Moderately to Severely Active 
Ulcerative Colitis 
Protocol Number: 
20170104 
Investigational Product: 
Efavaleukin Alfa 
Trade Name: 
Not applicable 
Sponsor 
Name of Sponsor: 
Amgen Inc. 
Address: 
One Amgen Center Drive, 
Thousand Oaks, CA 91320, USA 
Telephone 
Number: 
+1 (805) 447-1000
Protocol 
Approver 
Name: 
, MD, MPH 
Function: 
Vice President Global Development 
 
Key 
Sponsor 
Contact 
Name: 
, MD 
Address: 
One Amgen Center Drive, 
Thousand Oaks, CA 91320, US 
Telephone 
Number: 
Email Address: 
EudraCT Number / EUCT 
Number: 
2021-002537-41 / 2023-506004-93-00 
NCT Number: 
Not applicable 
Protocol Version Date: 
Document Version 
Date 
Original 
4 June 2021 
Amendment 1 
4 August 2021 
Superseded 
Amendment 1 
11 August 2021 
Amendment 2 
9 August 2022 
Superseded 
Amendment 2 
22 August 2022 
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Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
Date:  21 August 2024 
Page 2 of 131 
CONFIDENTIAL 
Amendment 3 
04 May 2023 
Amendment 4 
17 July 2024 
Superseded 
Amendment 4 
21 August 2024 
Data Elements Standards 
Version: 
8.0 
This protocol was developed, reviewed, and approved in &((47)&3(*<.9-2,*3H8
standard operating procedures.  This format and content of this protocol is aligned with 
Good Clinical Practice:  Consolidated Guidance (ICH E6). 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104  
Date:  21 August 2024 
Page 3 of 131 
CONFIDENTIAL  
 
 
Confidentiality Notice 
This document contains confidential information of Amgen Inc. 
This document must not be disclosed to anyone other than the site study staff and 
members of the institutional review board/independent ethics committee/institutional 
scientific review board or equivalent. 
The information in this document cannot be used for any purpose other than the 
evaluation or conduct of the clinical investigation without the prior written consent of 
Amgen Inc. 
If you have questions regarding how this document may be used or shared, call the 
Amgen Medical Information number:  US sites, 1- 800-77-AMGEN; Canadian sites, 
1-866-50-2,*3H8,*3*7&13:2'*7.39-*$"-805-447-1000. 
 
 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104  
Date:  21 August 2024 
Page 4 of 131 
CONFIDENTIAL  
 
 
 
I have read the attached protocol entitled A Phase 2, Dose-finding, Randomized, 
Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy 
of Efavaleukin Alfa Induction Therapy in Subjects with Moderately to Severely Active 
Ulcerative Colitis, dated 21 August 2024, and agree to abide by all provisions set forth 
therein.   
I agree to comply with the International Council for Harmonisation (ICH) Tripartite 
Guideline on Good Clinical Practice (GCP), Declaration of Helsinki, and applicable 
national or regional regulations/guidelines.   
I agree to ensure that Financial Disclosure Statements will be completed by: me 
(including, if applicable, my spouse or legal partner and dependent children) and my sub 
investigators (including, if applicable, their spouses or legal partners and dependent 
children) at the start of the study and for up to 1 year after the study is completed, if 
there are changes that affect my financial disclosure status. 
I agree to ensure that the confidential information contained in this document will not be 
used for any purpose other than the evaluation or conduct of the clinical investigation 
without the prior written consent of Amgen Inc. 
 
_______________________________ 
Signature 
 
_______________________________ ____________________________ 
Name of Investigator 
 
 
Date (DD Month YYYY) 
 
_______________________________ 
Title and Role of Investigator 
 
_______________________________ 
Institution Name 
 
_______________________________ 
Address and Telephone Number of Institution 
 
 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104  
Date:  21 August 2024 
Page 5 of 131 
CONFIDENTIAL  
 
 
Table of Contents 
Table of Contents ................................................................................................... 5 
1. 
Protocol Summary ................................................................................................ 10 
1.1 
Synopsis ................................................................................................... 10 
Sponsor Name: ..................................................................................................... 13 
1.2 
Study Schema ........................................................................................... 14 
1.3 
Schedule of Activities (SoA) ...................................................................... 15 
2. 
Introduction ........................................................................................................... 23 
2.1 
Study Rationale ......................................................................................... 23 
2.2 
Background ............................................................................................... 23 
2.2.1 
Disease ..................................................................................... 23 
2.2.1.1 
Limitations of Current Therapies ............................. 24 
2.2.1.2 
Regulatory T Cells and Interleukin-2 ....................... 25 
2.2.2 
Amgen Investigational Product Background:  
Efavaleukin Alfa ........................................................................ 26 
2.3 
Benefit/Risk Assessment ........................................................................... 26 
2.3.1 
COVID-19 .................................................................................. 28 
3. 
Objectives and Endpoints/Estimands .................................................................... 29 
4. 
Study Design ........................................................................................................ 33 
4.1 
Overall Design .......................................................................................... 33 
4.1.1 
Induction Period ........................................................................ 34 
4.1.2 
Long-term Treatment Period ...................................................... 35 
4.1.3 
Safety Follow-up Period ............................................................ 37 
4.2 
Patient Input into the Study Design ........................................................... 37 
4.3 
Justification for Dose ................................................................................. 37 
4.3.1 
Justification for Investigational Product Dose............................. 37 
4.4 
End of Study ............................................................................................. 39 
5. 
Study Population .................................................................................................. 39 
5.1 
Inclusion Criteria ....................................................................................... 40 
5.2 
Exclusion Criteria ...................................................................................... 42 
5.3 
Subject Enrollment .................................................................................... 46 
5.4 
Screen Failures ......................................................................................... 47 
5.5 
Eligibility Requirements for Progression to Long-term Treatment .............. 47 
6. 
Study Intervention ................................................................................................. 47 
6.1 
Study Interventions Administered .............................................................. 47 
6.1.1 
Investigational Products ............................................................ 47 
6.1.1.1 
Dose Administration and Schedule in the 
Induction Period ...................................................... 48 
6.1.1.2 
Dose Administration and Schedule in the 
Long-term Treatment Period ................................... 48 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104  
Date:  21 August 2024 
Page 6 of 131 
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6.1.2 
Medical Devices ........................................................................ 49 
6.1.3 
Other Protocol-required Therapies ............................................ 49 
6.1.4 
Other Intervention Procedures ................................................... 50 
6.1.4.1 
Home Health Care Visits ......................................... 50 
6.1.5 
Product Complaints ................................................................... 50 
6.1.6 
Excluded Treatments, Medical Devices, and/or 
Procedures During Study Period ............................................... 50 
6.2 
Dose Modification ...................................................................................... 51 
6.2.1 
Dose Treatment Group Study Escalation/De-
escalation and Stopping Rules .................................................. 51 
6.2.2 
Dosage Adjustments, Delays, Rules for Withholding or 
Restarting, Permanent Discontinuation ..................................... 51 
6.2.2.1 
Amgen Investigational Product:  
Efavaleukin Alfa ...................................................... 51 
6.2.3 
Hepatotoxicity Stopping and Rechallenge Rules ....................... 51 
6.3 
Preparation/Handling/Storage/Accountability ............................................ 51 
6.4 
Measures to Minimize Bias:  Randomization and Blinding ......................... 52 
6.4.1 
Method of Treatment Assignment .............................................. 52 
6.4.1.1 
Subject Randomization ........................................... 52 
6.4.2 
Blinding ..................................................................................... 52 
6.4.2.1 
Site Personnel Access to Individual 
Treatment Assignments .......................................... 52 
6.4.2.2 
Access to Individual Subject Treatment 
Assignments by Amgen or Designees ..................... 52 
6.5 
Treatment Compliance .............................................................................. 53 
6.6 
Treatment of Overdose ............................................................................. 53 
6.7 
Prior and Concomitant Treatment ............................................................. 53 
6.7.1 
Prior Treatment ......................................................................... 53 
6.7.2 
Concomitant Treatment ............................................................. 53 
6.7.2.1 
Induction Period ...................................................... 53 
6.7.2.2 
Long-term Treatment Period ................................... 54 
7. 
Discontinuation of Study Treatment and Subject 
Discontinuation/Withdrawal ................................................................................... 55 
7.1 
Discontinuation of Study Treatment........................................................... 55 
7.2 
Subject Discontinuation/Withdrawal from the Study .................................. 56 
7.2.1 
Reasons for Removal from Study .............................................. 56 
7.3 
Lost to Follow-up ....................................................................................... 56 
8. 
Study Assessments and Procedures .................................................................... 57 
8.1 
General Study Periods .............................................................................. 57 
8.1.1 
Screening, Enrollment and/or Randomization ............................ 57 
8.1.2 
Induction Period ........................................................................ 59 
8.1.3 
Long-term Treatment Period ...................................................... 59 
8.1.4 
Safety Follow-up Period ............................................................ 60 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104  
Date:  21 August 2024 
Page 7 of 131 
CONFIDENTIAL  
 
 
8.2 
General Assessments ............................................................................... 60 
8.2.1 
Informed Consent ...................................................................... 60 
8.2.2 
Demographics ........................................................................... 60 
8.2.3 
Medical History .......................................................................... 60 
8.2.4 
Physical Examination ................................................................ 60 
8.2.5 
Physical Measurements ............................................................ 60 
8.2.6 
Substance Abuse History .......................................................... 60 
8.2.7 
Columbia Suicide Severity Rating Scale .................................... 60 
8.3 
Efficacy Assessments ............................................................................... 61 
8.3.1 
Mayo Score (Total, Modified, and Partial) .................................. 61 
8.3.1.1 
Mayo Daily Symptom Diary ..................................... 62 
8.3.1.2 
Endoscopy .............................................................. 62 
8.3.1.3 
 ->8.(.&3H814'&188*882*39 ............................... 63 
8.3.2 
Histopathology via Mucosal Biopsy ........................................... 63 
8.3.3 
Clinical Outcome Assessments ................................................. 63 
8.3.3.2 
Inflammatory Bowel Disease 
Questionnaire .......................................................... 64 
8.3.3.3 
EQ-5D-5L ................................................................ 65 
8.3.3.4 
Patient Global Impression of Change ...................... 65 
8.3.3.5 
Patient Global Impression of Severity ...................... 65 
8.4 
Safety Assessments .................................................................................. 65 
8.4.1 
Vital Signs ................................................................................. 65 
8.4.2 
Electrocardiograms (ECGs) ....................................................... 66 
8.4.3 
Clinical Laboratory Assessments ............................................... 66 
8.4.3.1 
Tuberculosis Testing ............................................... 66 
8.4.3.2 
HIV Antibodies, Hepatitis B, and Hepatitis 
C Testing ................................................................. 67 
8.4.3.3 
Fecal Calprotectin, Fecal Lactoferrin, C 
Difficile Toxin and Enteric Pathogen 
Testing .................................................................... 67 
8.4.4 
Adverse Events and Serious Adverse Events ............................ 68 
8.4.4.1 
Time Period and Frequency for Collecting 
and Reporting Safety Event Information .................. 68 
8.4.4.2 
Method of Detecting Adverse Events and 
Serious Adverse Events .......................................... 69 
8.4.4.3 
Follow-up of Adverse Events and Serious 
Adverse Events ....................................................... 69 
8.4.4.4 
Regulatory Reporting Requirements for 
Safety Information ................................................... 69 
8.4.4.5 
Safety Monitoring Plan ............................................ 70 
8.4.4.6 
Pregnancy and Lactation ......................................... 70 
8.5 
Pharmacokinetic Assessments .................................................................. 71 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104  
Date:  21 August 2024 
Page 8 of 131 
CONFIDENTIAL  
 
 
8.6 
Pharmacogenetic Assessments (Optional Consent) .................................. 71 
8.7 
Antibody Testing Procedures .................................................................... 72 
8.8 
Biomarkers ................................................................................................ 73 
8.8.1 
Pharmacodynamic Assessments ............................................... 73 
8.8.2 
Biomarker Development ............................................................ 73 
8.8.3 
Biomarker Future Research ....................................................... 73 
8.9 
Medical Resource Utilization and Health Economics ................................. 74 
9. 
Statistical Considerations ...................................................................................... 74 
9.1 
Statistical Hypotheses ............................................................................... 74 
9.2 
Sample Size Determination ....................................................................... 74 
9.3 
Populations for Analysis ............................................................................ 75 
9.3.1 
Covariates ................................................................................. 75 
9.3.2 
Subgroups ................................................................................. 75 
9.4 
Statistical Analyses ................................................................................... 75 
9.4.1 
Planned Analyses ...................................................................... 76 
9.4.1.1 
Interim Analysis and Early Stopping 
Guidelines ............................................................... 76 
9.4.1.2 
Primary Analysis ..................................................... 76 
9.4.1.3 
Final Analysis .......................................................... 77 
9.4.2 
Methods of Analyses ................................................................. 77 
9.4.2.1 
General Considerations ........................................... 77 
9.4.2.2 
Efficacy Analyses .................................................... 77 
9.4.2.3 
Safety Analyses ...................................................... 78 
10. 
References ........................................................................................................... 80 
11. 
Appendices ........................................................................................................... 83 
11.1 
Appendix 1.  List of Abbreviations ............................................................. 83 
11.2 
Appendix 2.  Clinical Laboratory Tests ...................................................... 86 
11.3 
Appendix 3.  Study Governance Considerations ....................................... 89 
11.4 
Appendix 4.  Safety Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up and Reporting ....................................... 98 
11.5 
Appendix 5.  Contraceptive Guidance and Collection of 
Pregnancy and Lactation Information ...................................................... 106 
11.6 
Appendix 6.  Sample Storage and Destruction ........................................ 111 
11.7 
Appendix 7.  Hepatotoxicity Stopping Rules:  Suggested Actions 
and Follow-up Assessments and Study Treatment Rechallenge 
Guidelines ............................................................................................... 113 
11.8 
Appendix 8.  Prohibited Medications ....................................................... 117 
11.9 
Appendix 9.  Permitted Medications ........................................................ 119 
11.10 Appendix 10.  Mayo Scoring System for the Assessment of 
Ulcerative Colitis Activity ......................................................................... 120 
11.11 Appendix 11.  Country-specific Requirements ......................................... 121 
 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104  
Date:  21 August 2024 
Page 9 of 131 
CONFIDENTIAL  
 
 
 
List of Tables 
Table 1-1.  Schedule of Activities C Screening and Start of Induction 
Treatment Period .................................................................................... 15 
Table 1-2.  Schedule of Activities C Induction Period ..................................................... 18 
Table 1-3.  Schedule of Activities C Exploratory Long-term Treatment Period................ 20 
Table 1-4.  Schedule of Activities C Safety Follow-up .................................................... 22 
Table 6-1.  Investigational Product Administration:  Long-term Treatment 
Period ..................................................................................................... 49 
Table 11-1.  Analyte Listing ........................................................................................... 87 
Table 11-2.  DILI Potential Analyte Listing ..................................................................... 88 
Table 11-3.  Conditions for Withholding and/or Permanent Discontinuation of 
Amgen Investigational Product and Other Protocol-required 
Therapies Due to Potential Hepatotoxicity ............................................ 114 
Table 11-4.  EU Member States (Austria, Czech Republic, Italy, Poland, 
Germany, Hungary, Denmark, Finland, and Romania) 
Summary of Changes ........................................................................... 122 
Table 11-5.  Germany Summary of Changes ............................................................... 125 
Table 11-6.  France Summary of Changes .................................................................. 130 
List of Figures 
Figure 1-1.  Study Schema ............................................................................................ 14 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104  
Date:  21 August 2024 
Page 10 of 131 
CONFIDENTIAL  
 
 
1. 
Protocol Summary 
1.1 
Synopsis 
Protocol Title:  A Phase 2, Dose-finding, Randomized, Double-blind, 
Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of Efavaleukin 
Alfa Induction Therapy in Subjects with Moderately to Severely Active Ulcerative Colitis 
Short Protocol Title:  Safety and Efficacy of Efavaleukin Alfa in Subjects with 
Moderately to Severely Active Ulcerative Colitis 
Study Phase:  2 
Indication:  Ulcerative colitis (UC) 
Rationale 
This phase 2 dose-finding study will assess the safety and efficacy of induction therapy 
with efavaleukin alfa in subjects with moderately to severely active UC.  Efavaleukin alfa 
may be a viable treatment option for patients with moderately to severely active UC who 
have failed at least 1 of the following: conventional therapy (eg, immunomodulators, 
corticosteroids), biologic therapy, or targeted small molecule therapy (ie, Janus kinase 
[JAK] inhibitor). 
Benefit/Risk Assessment 
The safety of efavaleukin alfa has been evaluated in healthy subjects and in subjects 
with rheumatoid arthritis (RA), chronic graft versus host disease (cGvHD), and systemic 
lupus erythematosus (SLE).  See Section 2.3 for more information on these studies.  
Efavaleukin alfa has been well tolerated in clinical studies and has an acceptable safety 
profile.   
Based upon the totality of available safety data to date, the benefit/risk profile of 
efavaleukin alfa is favorable.  The benefit risk assessment detailed in Section 2.3 
supports the conduct of this phase 2 clinical trial in subjects with UC.   
!*+*7*3(*8-4:1)'*2&)*949-*1&9*89;*78.434+9-*3;*89.,&947H874(-:7*+47+:79-*7
safety data on efavaleukin alfa. 
Objective(s) and Endpoint(s)/Estimands 
 
Objectives 
Endpoints 
Primary 
 
To evaluate the effect of 
efavaleukin alfa on induction of 
clinical remission 
 
Clinical remission at week 12 
Primary Estimand 
Variable:  Clinical remission at week 12 
Estimator:  Difference in clinical remission rates 
Population:  All subjects with moderately to severely active UC with inadequate 
response, loss of response, or intolerance to at least 1 of the following: conventional 
therapy, biologics, or targeted small molecules, who are randomized. 
Treatments:  Each efavaleukin alfa dose group and placebo.   

Product:  Efavaleukin Alfa 
Protocol Number:  20170104  
Date:  21 August 2024 
Page 11 of 131 
CONFIDENTIAL  
 
 
UC = ulcerative colitis 
 
Overall Design 
This phase 2 dose-finding study is a multicenter, randomized, double-blind, 
placebo-controlled, parallel-group, 12-week induction study of efavaleukin alfa in 
subjects with moderately to severely active UC who have failed at least 1 of the 
following: conventional therapy (eg, immunomodulators, corticosteroids), biologic 
therapy, or targeted small molecule.  This study will be used to establish the efavaleukin 
alfa induction dose and maintenance dose/dosing regimens for continued development. 
After completing all screening procedures and meeting eligibility criteria, subjects will be 
randomized in a 1:1:1:1 ratio to receive placebo or one of 3 efavaleukin alfa doses.  
Randomization will be stratified by prior experience with at least 1 biologic or targeted 
small molecule (yes/no) and corticosteroid use at randomization (yes/no).  
Approximately 30 of enrolled subjects are allowed to be naïve to a biologic or targeted 
small molecule therapy.  Screening may be closed for subjects naïve to biologic or 
targeted small molecule therapy, if based on current enrolled subjects and those in 
screening, it is anticipated that enrolment of subjects naïve to a biologic or targeted 
small molecule will be greater than 30% of the total planned enrolment.  Subjects who 
Intercurrent event C composite variable strategy:  Subjects will be considered as not 
meeting the endpoint if they meet any of the following criteria prior to the week 12 visit: 
 
Initiation of or change in protocol-prohibited medication or concomitant UC 
medication 
 
A colectomy (partial or total) or an ostomy 
 
Discontinuation of investigational product 
Secondary 
 
To evaluate the effect of 
efavaleukin alfa on induction of 
clinical response 
 
Clinical response at week 12 
 
To evaluate the effect of 
efavaleukin alfa on induction of 
endoscopic remission 
 
Endoscopic remission at week 12 
 
To evaluate the effect of 
efavaleukin alfa on induction of 
symptomatic remission 
 
Symptomatic remission at 
week 12 
 
To evaluate the effect of 
efavaleukin alfa as induction 
therapy on combined endoscopic 
and histologic remission 
 
Combined endoscopic remission 
and histologic remission of the 
colon tissue at week 12 
 
To evaluate the effect of 
efavaleukin alfa as induction 
therapy on change in histological 
score 
 
Change from baseline in 
histological score at week 12 as 
measured by Geboes score 
 
To evaluate the safety and 
tolerability of efavaleukin alfa 
 
Treatment-emergent adverse 
events 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104  
Date:  21 August 2024 
Page 12 of 131 
CONFIDENTIAL  
 
 
complete the 12-week induction period will have the option to continue treatment in an 
exploratory long-term treatment period if in the opinion of the investigator they may 
benefit from continued treatment.  The long-term treatment period will explore the safety 
and efficacy of continued treatment with efavaleukin alfa for up to 40 weeks (total of up 
to 52 weeks of treatment).  For a full list of study procedures, including the timing of each 
procedure, please refer to Section 8 and the Schedule of Activities (Section 1.3). 
Interim analyses will be performed to assess futility (Section 9.4.1.1). 
An independent Data Monitoring Committee (DMC) will oversee safety and overall 
conduct of the study (Section 11.3).  The first 2 DMC meetings will occur after the first 
20 subjects randomized have had the opportunity to complete the
and week 12 
visits.  Thereafter the DMC will plan to meet approximately every 3 months until Amgen 
is unblinded at the primary analysis.  After Amgen is unblinded, the DMC will plan to 
meet every 6 months.  Ad hoc meetings can be scheduled as needed.  The DMC will 
also review all available safety and efficacy data for interim analyses (see 
Section 9.4.1.1 for timepoints). 
Study Assessments and Procedures 
Efficacy assessments include the modified Mayo score using centrally read endoscopies 
and mucosal biopsies at screening, week 12, and week 52 (or at early termination, as 
applicable), partial Mayo scores, biomarkers (fecal calprotectin, fecal lactoferrin, and 
high sensitivity C-reactive protein [hsCRP]), and patient reported outcomes (PROs).  
Safety assessments include physical examination, collection of adverse events and 
serious adverse events, chemistry, hematology, coagulation, urinalysis, pregnancy 
testing as applicable, and immunogenicity.  This study also includes pharmacodynamic 
(PD) and pharmacokinetic (PK) assessments. 
Number of Subjects 
Approximately 240 subjects will be enrolled, 60 subjects per treatment group. 
Summary of Subject Eligibility Criteria 
The study will enroll men and women 18 to 80 years of age (19 to 80 in South Korea) 
with a diagnosis of UC for 
 3 months prior to enrollment.  Subjects must have 
moderately to severely active UC defined by a modified Mayo score of 5 to 9, with a 
centrally read endoscopic subscore 
 2.  Subjects must have experienced inadequate 
response or loss of response or intolerance to at least 1 conventional therapy or biologic 
or targeted small molecule therapy.  Subjects must have stable doses of oral 
5-aminosalicylates (ASA; stable dose for 
 2 weeks), oral corticosteroids (dose must be 
 20 mg/day prednisone or its equivalent and must have been stable for 
 2 weeks), 
budesonide (extended release tablets 9 mg/day; stable dose for 
 2 weeks), 
beclomethasone dipropionate (gastro-resistant prolonged-release tablet 5 mg/day; 
stable dose for 
 2 weeks), and conventional immunomodulators (azathioprine, 
6-mercaptopurine, methotrexate; stable dose for 
 12 weeks).  Exclusion criteria include 
&).&,348.84+74-3H8).8*&8*47 indeterminate colitis, UC limited to the rectum, clinical 
signs of fulminant colitis, toxic megacolon, or patients with a history of colectomy. 
For a full list of eligibility criteria, please refer to Section 5.1 to Section 5.2. 
Treatments 
Efavaleukin alfa and placebo will be manufactured and packaged by Amgen Inc. and 
distributed using Amgen clinical study drug distribution procedures.  Both are liquid 
formulations presented in highly similar glass vials and stored in the same manner.  

Product:  Efavaleukin Alfa 
Protocol Number:  20170104  
Date:  21 August 2024 
Page 13 of 131 
CONFIDENTIAL  
 
 
Efavaleukin alfa or placebo will be administered by subcutaneous (SC) injection
 
 
In the induction period, 4 dose groups are planned with a placebo group and 
3 efavaleukin alfa dose groups: 
g 
g
 and 
g
  
In the long-term treatment period, subjects randomized to efavaleukin alfa during 
induction will remain on the same blinded dose throughout the long-term treatment 
period (both subjects who achieved clinical response at week 12 and those who did not 
achieve clinical response at week 12).  Subjects randomized to placebo who achieved 
clinical response at week 12 will remain on placebo.  Subjects randomized to placebo 
who did not achieve clinical response at week 12 will receive efavaleukin alfa 
g
in a blinded manner during the long-term treatment period. 
For a full description of the investigational product doses, please refer to Section 6.1.1. 
Statistical Considerations 
The full analysis set will be used for analysis of the primary and secondary efficacy 
endpoints and will include all subjects randomized.  The safety analysis set will include 
all randomized subjects who received at least 1 dose of investigational product. 
Nominal p-values will be reported for the primary and secondary efficacy endpoints, with 
no adjustment for multiplicity. 
The primary estimand will be analyzed using logistic regression to test the difference in 
clinical remission rates between efavaleukin alfa dose and placebo (Ge et al, 2011).  
The stratification factors as captured in the interactive response technology (IRT) will be 
included as covariates.  The estimate of the risk difference between each efavaleukin 
alfa dose and placebo, the corresponding 2-sided 95 Wald confidence interval, and the 
p-value obtained from the logistic regression model will be provided.  Missing primary 
endpoint data will be imputed using nonresponder imputation. 
The primary analysis will occur when all subjects have had the opportunity to complete 
the week 12 visit.  All primary and secondary objectives will be evaluated at the primary 
analysis. 
For a full description of statistical analysis methods, please refer to Section 9. 
Statistical Hypotheses 
The primary hypothesis is that at least 1 efavaleukin alfa dose will have greater efficacy 
compared to placebo as measured by clinical remission rates at week 12 in subjects with 
moderately to severely active UC. 
Sponsor Name: 
 Amgen Inc. 
 

Product:  Efavaleukin Alfa
Protocol Number:  20170104
Date:  21 August 2024
Page 14 of 131
CONFIDENTIAL
1.2
Study Schema
Figure 1-1.  Study Schema
a Primary analysis for safety and efficacy.  Assessment of clinical remission and clinical response using the modified Mayo Score in accordance with the Schedule of 
Activities (Table 1-1 and Table 1-2) and planned study objectives (Section 3).
b Eligible subjects will have the option to continue to be treated in an exploratory long-term treatment period for up to 40 additional weeks of treatment if in the opinion 
of the investigator they may benefit from continued treatment (total of up to 52-weeks of treatment).
CCI

Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
Date:  21 August 2024 
Page 15 of 131 
CONFIDENTIAL 
 
1.3 
Schedule of Activities (SoA) 
Table 1-1.  Schedule of Activities  Screening and Start of Induction Treatment Period 
DAY 
Screening 
Randomization and Start of Induction Treatment Period 
-35 to -1 
-14 to -5 
1 
3 to 4 
 
 
 
Pre-randomization 
Pre-dose 
Dose 
6 to 24 hr 
postdose 
48 to 96 hr 
postdose 
GENERAL AND SAFETY ASSESSMENTS 
Informed Consent 
X 
 
 
 
 
 
 
Inclusion and Exclusion Criteria 
X 
 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Physical Examination 
X 
 
 
X 
 
 
 
Height 
X 
 
 
 
 
 
 
Weight 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Substance Abuse History 
X 
 
 
 
 
 
 
C-SSRS 
X 
 
 
 
 
 
 
Vital Signs 
X 
 
X 
 
 
X 
X 
ECG 
X 
 
 
 
 
X 
X 
Prior/ Onstudy UC Related 
Hospitalizations/Surgeries 
X 
 
 
 
 
 
 
Adverse Events 
 
 
 
 
X 
 
 
Serious Adverse Eventsa 
X 
 
 
 
 
 
 
Prior/Concomitant Therapies Review 
X 
 
 
 
 
 
 
Randomizationb 
 
 
 
X 
 
 
 
LABORATORY ASSESSMENTS 
Pregnancy Testc 
Serum 
 
Urine 
 
 
 
 
FSH (postmenopausal women only) 
X 
 
 
 
 
 
 
Tuberculosis Screeningd 
X 
 
 
 
 
 
 
HIV, Hepatitis B and C Screeninge 
X 
 
 
 
 
 
 
Hematology 
X 
 
 
X 
 
 
 
Chemistry 
X 
 
 
X 
 
 
 
Urinalysis 
X 
 
 
X 
 
 
 
Coagulation 
 
 
 
X 
 
 
 
hsCRP 
 
 
 
X 
 
 
 
C. difficile toxin and enteric pathogen testing 
X 
 
 
 
 
 
 
Fecal Calprotectinf 
 
 
 
X 
 
 
 
Fecal Lactoferrinf 
 
 
 
X 
 
 
 
IMMUNOGENICITY ASSESSMENTS 
Anti-efavaleukin alfa antibody 
 
 
 
X 
 
 
 
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Table 1-1.  Schedule of Activities  Screening and Start of Induction Treatment Period 
DAY 
Screening 
Randomization and Start of Induction Treatment Period 
-35 to -1 
-14 to -5 
1 
3 to 4 
 
 
 
Pre-randomization 
Pre-dose 
Dose 
6 to 24 hr 
postdose 
48 to 96 hr 
postdose 
BIOMARKER ASSESSMENTS 
Biomarker Development Sample 
 
 
 
X 
 
X 
X 
Lymphocyte Subset 
 
 
 
X 
 
 
 
Biomarker Mucosal Biopsy Sample 
 
X 
 
 
 
 
 
PHARMACOGENETIC ASSESSMENTS 
Pharmacogenetic Blood Sampleg 
 
 
 
X 
 
 
 
PHARMACOKINETIC ASSESSMENTS 
Pharmacokinetic Blood Sample 
 
 
 
X 
 
X 
X 
EFFICACY ASSESSMENTS 
Modified Mayo Score Review 
 
 
X 
 
 
 
 
Partial Mayo Score Review 
 
X 
 
X 
 
 
 
Endoscopy 
 
Xh 
 
 
 
 
 
Mucosal Biopsy (histopathology) 
 
X 
 
 
 
 
 
CLINICAL OUTCOME ASSESSMENTS 
Physician Global Assessment 
 
X 
 
X 
 
 
 
Mayo Daily Symptom Diary (daily) 
X 
 
 
 
 
 
 
IBDQ 
 
 
 
X 
 
 
 
PGIS 
 
 
 
X 
 
 
 
EQ-5D-5L 
 
 
 
X 
 
 
 
STUDY TREATMENT 
Investigational Product Administration 
 
 
Page 2 of 2 
C-SSRS = Columbia Suicide Severity Rating Scale; ECG = electrocardiogram; EQ-5D-5L = EuroQol-5-Dimension 5 levels; FSH = follicle stimulating hormone; 
HIV = human immunodeficiency virus; hsCRP = high sensitivity C-reactive protein; IBDQ = inflammatory bowel disease questionnaire; PGIS = Patient Global 
Impression of Severity; UC = ulcerative colitis;
a After end of study, serious adverse events suspected to be related to investigational product will be reported to Amgen.  Please refer to Section 8.4.4.1.3 for 
additional details. 
b Randomization will occur after confirmation of all eligibility criteria.  The maximum time between initiation of screening and randomization is 35 calendar days.  A 
subject must be in screening for at least 14 days prior to day 1 to enable a minimum of 7 days of Mayo daily symptom diary collection and receipt of results from the 
centrally read endoscopy. 
c For women of childbearing potential only:  serum pregnancy test is to be performed at screening (central laboratory) and urine pregnancy test is to be performed at all 
other indicated time points (local laboratory). 
d Refer to Section 8.4.3.1. 
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e Refer to Section 8.4.3.2. 
f Sites to provide the stool sample container for fecal calprotectin and fecal lactoferrin at the endoscopy visit; if the subject is eligible after endoscopy and scheduled for 
randomization, then the site can contact the subject to collect a stool sample the day before or morning of the Day 1 visit. 
g DNA will be extracted only if subject provides additional consent for pharmacogenetics testing. 
h Subjects who do not have a colonoscopy report available as source documentation at screening to confirm eligibility per inclusion criterion 105, will have a 
colonoscopy instead of rectosigmoidoscopy as the screening endoscopy for the study.  Subjects with a combined stool frequency and rectal bleeding subscore 

 2 (using the average of the 3 most recent days in the 7 days prior to initiation of bowel preparation for the screening endoscopy) can proceed with endoscopy 
(Section 8.3.1.2). 
i At visits on which investigational product is administered, all assessments must be completed in advance of investigational product administration unless otherwise 
noted.  The dose of investigational product must be given within the window of time specified for the scheduled time point.  If that window is missed, that dose will not 
be administered, and the next dose administered at the next scheduled dosing date.  Any 2 consecutive doses of investigational product must be at least 7 days 
apart. 
 
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Table 1-2.  Schedule of Activities  Induction Period 
WEEK
Induction Treatment Period (Weeks) 
W12 
STUDY DAY 	 VISIT WINDOW 
 	 5 
 	 1 
 	 5 
 	 5 
 	 5 
 
6 to 24 hr 
post dose 
 
48 to 96 hr 
post dose 
 	 5 
85 	 5 
GENERAL AND SAFETY ASSESSMENTS 
Weight 
 
 
 
 
 
 
 
 
X 
Vital Signs 
X 
X 
X 
X 
X 
 
 
X 
X 
ECGa 
 
 
 
 
 
 
 
 
X 
Prior/ Onstudy UC Related 
Hospitalizations/Surgeries 
 
 
 
 
 
 
 
 
 
Adverse Events 
 
 
 
 
 
 
 
 
 
Serious Adverse Eventsb 
 
 
 
 
 
 
 
 
 
Prior/Concomitant Therapies Review 
 
 
 
 
 
 
 
 
 
LABORATORY ASSESSMENTS 
Pregnancy Testc 
 
 
Urine 
 
Urine 
 
 
 
Urine 
Hematology 
X 
 
X 
 
X 
 
 
 
X 
Chemistry 
X 
 
X 
 
X 
 
 
 
X 
Urinalysis 
 
 
X 
 
X 
 
 
 
X 
hsCRP 
 
 
X 
 
X 
 
 
 
X 
Fecal Calprotectin 
 
 
X 
 
X 
 
 
 
X 
Fecal Lactoferrin 
 
 
X 
 
X 
 
 
 
X 
IMMUNOGENICITY ASSESSMENTS 
Anti-efavaleukin alfa antibody 
X 
 
X 
 
X 
 
 
 
X 
BIOMARKER ASSESSMENTSa 
Biomarker Development Sample 
X 
X 
 
X 
X 
X 
X 
 
X 
Lymphocyte Subset 
X 
X 
 
X 
 
 
 
 
X 
Biomarker Mucosal Biopsy Sample 
 
 
 
 
 
 
 
 
X 
PHARMACOKINETIC ASSESSMENTSa 
Pharmacokinetic Blood Sample 
 
 
 
 
X 
X 
X 
 
X 
EFFICACY ASSESSMENTS 
Modified Mayo Score Review 
 
 
 
 
 
 
 
 
X 
Partial Mayo Score Review 
X 
X 
X 
X 
X 
 
 
X 
X 
Endoscopy 
 
 
 
 
 
 
 
 
X 
Mucosal Biopsy (histopathology) 
 
 
 
 
 
 
 
 
X 
Page 1 of 2 
Footnotes defined on the last page of the table. 
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Table 1-2.  Schedule of Activities  Induction Period 
WEEK
Induction Treatment Period (Weeks) 
W12 
STUDY DAY 	 VISIT WINDOW 
 	 5 
 	 1 
 	 5 
 	 5 
 	 5 
6 to 24 hr 
post dose 
 
48 to 96 hr 
post dose 
 	 5 
85 	 5 
CLINICAL OUTCOME ASSESSMENTS 
Physician Global Assessment 
X 
X 
X 
X 
X 
 
 
X 
X 
Mayo Daily Symptom Diary (daily) 
 
 
 
 
 
 
 
 
 
IBDQ 
 
 
X 
 
X 
 
 
 
X 
PGIS 
X 
 
X 
 
X 
 
 
 
X 
PGIC 
 
 
X 
 
X 
 
 
 
X 
EQ-5D-5L 
 
 
X 
 
X 
 
 
 
X 
STUDY TREATMENT 
Investigational Product Administrationd 
Investigational Product Administration C 
Long-term treatment 
Page 2 of 2 
ECG = electrocardiogram; EQ-5D-5L = EuroQol-5-Dimension 5 levels; hsCRP = high sensitivity C-reactive protein; IBDQ = inflammatory bowel disease questionnaire; 
PGIC = Patient Global Impression of Change; PGIS = Patient Global Impression of Severity; UC = ulcerative colitis; 
a If permitted by local regulations, the investigator may utilize a qualified home health care service provider, approved by sponsor, for collection of PK, biomarker 
samples, and ECG on visits without a scheduled administration of investigational product (See Section 6.1.4.1). 
b After end of study, serious adverse events suspected to be related to investigational product will be reported to Amgen.  Please refer to Section 8.4.4.1.3 for 
additional details. 
c For women of childbearing potential only:  serum pregnancy test is to be performed at screening (central laboratory) and urine pregnancy test is to be performed at all 
other indicated time points (local laboratory). 
d At visits on which investigational product is administered, all assessments must be completed in advance of investigational product administration unless otherwise 
noted.  The dose of investigational product must be given within the window of time specified for the scheduled time point.  If that window is missed, that dose will not 
be administered, and the next dose administered at the next scheduled dosing date.  Any 2 consecutive doses of investigational product must be at least 7 days 
apart. 
f Investigational product administration for subjects continuing in the long-term treatment will commence at the week 12 visit for the first dose (W12).  For week 12 
investigational product administration, the dosing window is up to  3 days after the week 12 visit to allow for dosing on a separate day from the endoscopy.  
 
 
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Table 1-3.  Schedule of Activities  Exploratory Long-term Treatment Period 
WEEK 
Long-term Treatment Period 
W52/
ETa 
STUDY DAY 	 VISIT 
WINDOW 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
365 
	 5 
GENERAL AND SAFETY ASSESSMENTS 
Weight 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECGb 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
Prior/ Onstudy UC Related 
Hospitalizations/Surgeries 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse Events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serious Adverse Eventsc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior/Concomitant 
Therapies Review 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LABORATORY ASSESSMENTS 
Pregnancy Testd 
 
Urine 
 
Urine 
 
Urine 
 
Urine 
 
Urine 
 
Urine 
 
Urine 
 
Urine 
 
Urine 
 
Urine 
Hematology 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
X 
Chemistry 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
X 
Urinalysis 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
 
 
 
 
X 
Fecal Calprotectin 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
IMMUNOGENICITY ASSESSMENTS 
Anti-efavaleukin alfa 
antibody 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
BIOMARKER ASSESSMENTSb g 
Biomarker Development 
Sample 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
Lymphocyte Subset 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
Biomarker Mucosal Biopsy 
Sample 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
EFFICACY ASSESSMENTS 
Partial Mayo Score Review 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Endoscopy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Xa 
Mucosal Biopsy 
(histopathology) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
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Table 1-3.  Schedule of Activities  Exploratory Long-term Treatment Period 
WEEK 
Long-term Treatment Period 
W52/
ETa 
STUDY DAY 	 VISIT 
WINDOW 
 	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
	 5 
365 
	 5 
CLINICAL OUTCOME ASSESSMENTS 
Physician Global 
Assessment 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Mayo Daily Symptom Diary 
(daily) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IBDQ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
PGIS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
PGIC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
EQ-5D-5L 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
STUDY TREATMENT 
Investigational Product 
Administratione 
Page 2 of 2 
ECG = electrocardiogram; ET = Early termination visit; EQ-5D-5L = EuroQol-5-Dimension 5 levels; hsCRP = high sensitivity C-reactive protein; IBDQ = inflammatory 
bowel disease questionnaire; PGIC = Patient Global Impression of Change; PGIS = Patient Global Impression of Severity; UC = ulcerative colitis; 
a An ET is required for all subjects who discontinue the study completely prior to week 52.  If a subject undergoes early termination soon after having their screening or 
week 12 endoscopy, the need for an ET endoscopy should be discussed with the Amgen physician.  
b If permitted by local regulations, the investigator may utilize a qualified home health care service provider, approved by sponsor, for collection of PK, biomarker 
samples, and ECG on visits without a scheduled administration of investigational product (See Section 6.1.4.1). 
c After end of study, serious adverse events suspected to be related to investigational product will be reported to Amgen.  Please refer to Section 8.4.4.1.3 for 
additional details. 
d For women of childbearing potential only:  serum pregnancy test is to be performed at screening (central laboratory) and urine pregnancy test is to be performed at all 
other indicated time points (local laboratory). 
e At visits on which investigational product is administered, all assessments must be completed in advance of investigational product administration unless otherwise 
noted.  The dose of investigational product must be given within the window of time specified for the scheduled time point.  If that window is missed, that dose will not 
be administered, and the next dose administered at the next scheduled dosing date.  Any 2 consecutive doses of investigational product must be at least 7 days 
apart. 
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g Blood samples must be collected prior to administration of investigational product. 

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Table 1-4.  Schedule of Activities  Safety Follow-up 
 
Safety Follow-upa 
Week  
Study Day 	 Visit Window 
 	 5 days 
GENERAL AND SAFETY ASSESSMENTS 
 
Vital Signs 
X 
UC Related Hospitalizations/Surgeries 
X 
Adverse Events 
X 
Serious Adverse Eventsb 
X 
Concomitant Therapies Review 
X 
LABORATORY ASSESSMENTS 
 
Pregnancy Test 
Urine 
Hematology 
X 
IMMUNOGENICITY ASSESSMENTS 
 
Anti-efavaleukin alfa antibody 
X 
UC = ulcerative colitis 
b After end of study, serious adverse events suspected to be related to investigational product will be reported to Amgen.  Please refer to Section 8.4.4.1.3 for 
additional details. 
 
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2. 
Introduction 
2.1 
Study Rationale 
Regulatory T cells (Tregs) play a vital role in countering inflammatory processes in the 
gut and are integral to maintenance of mucosal homeostasis (Bollrath and Powrie, 
2013).  Efavaleukin alfa is an interleukin-2 (IL-2) mutein Fc fusion protein that has been 
developed to preferentially expand Tregs in patients with inflammatory diseases, 
including ulcerative colitis (UC).  Support for the role of IL-2 in the treatment of UC 
comes from a recent clinical study of low dose IL-2, in which clinical response or 
remission was demonstrated in 9 of 15 subjects with moderate to severe UC after 
8 weeks of treatment (Allegretti et al, 2020).  Study 20170104 is a phase 2 dose-finding, 
multicenter, randomized, double-blind, placebo-controlled, parallel-group study that will 
evaluate the safety and efficacy of efavaleukin alfa to induce remission in subjects with 
moderately to severely active UC who have experienced inadequate response, loss of 
response, or intolerance to at least 1 of the following: conventional therapy (eg, 
corticosteroids, immunomodulators), biologic, or targeted small molecule therapy (eg, 
Janus kinase [JAK] inhibitors).  Subjects who complete the 12-week induction period will 
have the option to enter an exploratory long-term treatment period if in the opinion of the 
investigator they may benefit from continued treatment.  The long-term treatment period 
will explore the safety and efficacy of continued treatment with efavaleukin alfa for up to 
40 weeks (total of 52 weeks of treatment).  Efavaleukin alfa may be a viable treatment 
option for patients with moderately to severely active UC who have failed at least 1of the 
following: conventional (eg, immunomodulators, corticosteroids), biologic, or targeted 
small molecule therapies.  There is clear unmet medical need in this broad patient 
population (Section 5.1), which will be the patient population for this study. 
2.2 
Background 
2.2.1 
Disease 
Ulcerative colitis is a chronic inflammatory bowel disease (IBD) with symptoms that 
include abdominal pain, bloody diarrhea, and fecal urgency, which can occur without 
warning, placing a significant burden on daily life.  Ulcerative colitis most commonly 
affects adults 30 to 40 years of age, with approximately 20 of patients presenting 
before age 20 (Kelsen and Baldassano, 2008).  The incidence and prevalence of UC 
have been increasing over time worldwide (Ungaro et al, 2017).  The estimated United 
States incidence of UC is 9 to 12 cases per 100 000 persons per year, and the estimated 
prevalence is 205 to 240 cases per 100 000 persons (Danese and Fiocchi, 2011).  The 
incidence of UC in Europe ranges from 0.9 to 24.3 per 100 000 person-years.  The 

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highest incidence rates are observed in Scandinavia and the United Kingdom, while the 
lowest rates are seen in southern and Eastern Europe D suggesting a 
northwest/southeast gradient in IBD incidence (Burisch et al, 2013).  The prevalence of 
UC in Europe varies from 2.4 to 294 cases per 100 000 persons.  Extrapolating these 
numbers for the total European population indicates that there may be up to 2.1 million 
persons with UC in Europe (Burisch, et al, 2013).  In patients with UC, there is an 
increased risk of colorectal cancer compared with the general population, with risk 
factors such as long duration of disease, extensive colonic involvement, severe 
inflammation and epithelial dysplasia, and childhood-onset disease.  The goals of 
treatment in UC are to induce and maintain clinical response and endoscopic remission 
to prevent disability, colectomy, and colorectal cancer (Ungaro et al, 2017). 
2.2.1.1 
Limitations of Current Therapies 
In patients with mild to moderate disease severity, conventional treatment typically 
consists of oral or topical aminosalicylates (5-ASAs) or topical steroids for induction of 
remission and oral and/or topical 5-ASAs for maintenance (Rubin et al 2019).  
5-aminosalicyclic acid (5-ASA), a common first line therapy has been shown to be 
superior to placebo, yet a meta-analysis of 53 studies reported that 71 of the patients 
who initiated 5-ASA failed induction (Wang et al, 2016).  In patients that are refractory to 
5-ASA therapy or topical steroids, oral steroids can be used to induce remission (Rubin 
et al, 2019).  However, steroids are not indicated for maintenance therapy in UC 
because of unwanted side effec98949-**=9*399-&9E(479.(489*74.)-+7**7*2.88.43F.8&
frequent treatment goal in clinical guidelines (Rubin et al, 2019; Ford et al, 2011). 
Patients with moderate to severe disease are those who are dependent on or refractory 
to corticosteroids, have severe endoscopic disease activity (presence of ulcers), or are 
at high risk of colectomy.  Advanced therapies for the treatment of moderately to 
severely active UC include immunosuppressants (eg, azathioprine and 6-
mercaptopurine), biologic therapies such as anti-TNF inhibitors, anti-integrins (ie, 
vedolizumab), and interleukin-12 and -23 antagonists (ie, ustekinumab) as well as small 
molecule JAK inhibitors (eg, tofacitinib) (Danese et al, 2014).  However, even with these 
therapies, a large percentage of patients are not able to achieve and/or maintain 
remission.  A meta-analysis of 7 studies showed that 55 and 23 of subjects with UC 
who initiated an anti-TNF biologic responded and entered remission initially and that 
treatment response and remission were maintained in 39 and 24 of the subjects, 
respectively (Stidham et al, 2014).  While these rates compared favorably to those for 

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placebo, they suggest that about half of the subjects failed to respond initially and that 
61 of the initial responders lost their response over time.  Similar data have been 
reported for vedolizumab; in a pivotal study of 374 subjects with UC, 47.1 and 16.9 
achieved clinical response and clinical remission respectively at week 6 (Feagan et al, 
2013).  Finally, tofacitinib, an oral small molecule JAK inhibitor, presents as another 
option which compared favorable to placebo among patients with mild and moderate UC 
(Sandborn et al, 2017).  In 2 identical pivotal trials of tofacitinib (OCTAVE 1 and 2), 
induction of remission at week 8 was achieved in 18.5% and 16.6% of patients treated 
with tofacitinib compared to 8.2% and 3.6% of patients treated with placebo (Sandborn 
et al, 2017). 
Treatment options narrow significantly in patients with moderately to severely active UC 
who fail their first biologic therapy, which has been linked to a number of potential 
causes, including development of anti-drug antibody to anti-TNF biologic and 
vedolizumab (Mosli et al, 2015; Yarur et al, 2015).  In the OCTAVE Induction 1 and 2 
studies of tofacitinib, only 12 of the patients with prior anti-TNF biologic use entered 
remission at 8 weeks, compared with 23 in anti-TNF biologic naïve patients (Sandborn 
et al, 2017). 
Other limitations of available UC agents include the time required for response (eg, 
anti-integrins can take up to 6 months for maximum benefit to be seen) (Tripathi and 
Feuerstein, 2019). 
While treatment options are available for UC, there continues to be unmet need for new 
therapies with better safety and efficacy, particularly for achieving long term, steroid-free, 
remission and combined endoscopic and histologic remission. 
2.2.1.2 
Regulatory T Cells and Interleukin-2 
Regulatory T cells are a subset of CD4 T cells that suppress inflammation.  
Interleukin-2, a multi-functional cytokine produced predominantly by activated CD4 
T cells, is a key growth factor for Tregs and is essential for Treg maintenance, survival, 
and metabolism (Boyman and Sprent, 2012; Malek and Castro, 2010).  A loss of 
homeostatic balance between Treg and other lymphocytes is considered a causative 
factor in many inflammatory conditions.  In recent clinical studies, increasing Tregs with 
low dose recombinant IL-2 (Proleukin [aldesleukin]) has yielded promising results in 
patients with inflammatory diseases, including chronic graft versus host disease 
(cGvHD), systemic lupus erythematosus (SLE), hepatitis C virus vasculitis, and UC 

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(Allegretti et al, 2020; Rosenzwajg et al, 2019; Koreth et al, 2016; Humrich et al, 2015; 
Matsuoka et al, 2013; Koreth et al, 2011; Saadoun et al, 2011). 
Regulatory T cells play a vital role in countering inflammatory processes in the gut and 
are integral to maintenance of mucosal homeostasis (Bollrath and Powrie, 2013).  
Ulcerative colitis is associated with genetic polymorphisms in the IL-2 gene as well as 
the IL-10 gene, a suppressive cytokine produced by Tregs (Amgen internal data; 
Anderson et al, 2011; Festen et al, 2009).  An open-label, single group, phase 1b/2a 
study of daily SC administration of low dose IL-2 was recently performed in subjects with 
moderate-to-severely active UC (Allegretti et al, 2020).  Three sequentially increasing 
dose levels were tested (dose A:  0.3x106 IU/m2/day, dose B:  1x106 IU/m2/day, or 
dose C:  1.5x106 IU/m2/day) and Treg expansion was observed in all dosing cohorts, but 
Tcon activation was observed at the highest dose.  Overall, 41.6 (10/24) of subjects 
achieved either clinical response or remission, after 8 weeks of treatment, as assessed 
by Mayo score, including 60 (9/15) of subjects in the dose B cohort alone.  Low dose 
IL-2 was generally well tolerated; the most frequently reported adverse events included 
injection site reactions and malaise (Allegretti et al, 2020).  These data provided 
preliminary evidence that expansion of Tregs using low dose IL-2 may ameliorate 
disease in UC patients. 
2.2.2 
Amgen Investigational Product Background:  Efavaleukin Alfa 
Efavaleukin alfa is an IL-2 mutein Fc fusion protein that has been developed to 
preferentially expand Tregs in patients with inflammatory diseases.  Preclinical in vitro 
and in vivo studies have demonstrated that efavaleukin alfa exhibits greater selectivity 
for inducing Treg expansion over the expansion of other T cells and natural killer cells, 
relative to low dose recombinant IL-	7*+*794*+&;&1*:0.3&1+&3;*89.,&947H874(-:7*
for more details).  This greater selectivity of efavaleukin alfa may provide for greater 
efficacy and a wider therapeutic margin in inflammatory diseases relative to low dose 
recombinant IL-2 based modalities and, therefore, supports the investigation of 
efavaleukin alfa for the treatment of UC. 
A detailed description of the chemistry, pharmacology, and safety of efavaleukin alfa is 
574;.)*).39-*3;*89.,&947H874(-:7* 
2.3 
Benefit/Risk Assessment 
Treatment of moderately to severely active UC has evolved in recent years.  Progress 
has been made with the introduction of several new drug classes, including the 
anti-integrin vedolizumab, the interleukin-12 and -23 antagonist ustekinumab, and the 

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JAK-inhibitor tofacitinib, which have led to a significant improvement in response and 
remission rates (Danese et al, 2014). 
Ulcerative colitis is characterized by a recurring pattern of remission and relapse that 
can progress to extensive inflammation of the colon, resulting in significant morbidity.  
Approximately one-third (31%) of patients with limited UC at diagnosis will have disease 
extension by 10 years (Roda et al, 2017).  The 5-year and 10-year cumulative risk of 
colectomy is 10 to 15 (Fumery et al, 2018).  The goal of treatment for moderately to 
severely active UC is to achieve resolution of rectal bleeding, normalization of bowel 
habits, and mucosal healing in order to delay UC-associated complications such as 
colectomy and colon cancer, and to maintain an acceptable health related quality of life 
(Ungaro et al, 2017).  Investigational agents that utilize both novel targets and 
mechanisms of action, especially those that have shown clinical activity in first in human 
studies, have the potential to achieve these goals, particularly in patients with a high 
unmet need after their disease has progressed following treatment with available 
standard-of-care therapies. 
Regulatory T cells play a vital role in countering inflammatory processes in the gut and 
are integral to maintenance of mucosal homeostasis (Bollrath and Powrie, 2013).  With 
its novel mechanism of action, efavaleukin alfa is being developed for the treatment of 
UC, as it: a) exhibits greater selectivity for inducing Treg expansion over the expansion 
of other T cells and NK cells, relative to low dose recombinant IL-2, b) may provide 
greater efficacy and a wider therapeutic margin in inflammatory diseases relative to low 
dose recombinant IL-2-based modalities, c) offers less frequent dosing and greater 
convenience compared with low dose IL-2 and d) may have an improved safety and 
tolerability profile over existing UC therapies.  In addition, clinical experience with low 
dose IL-2 in subjects with UC has provided proof of concept support for this approach. 
The safety of efavaleukin alfa has been evaluated in healthy subjects and Phase 1 
studies of subjects with rheumatoid arthritis (RA), cGvHD and SLE.  Cumulative data 
from completed and ongoing Phase 1 clinical studies conducted since the beginning of 
the development program through 26 April 2022 include 167 subjects who have been 
exposed to at least 1 dose of efavaleukin alfa.  Single doses of up to 
 g have been 
studied in healthy subjects (82 subjects).  Repeated doses of up to 
 g 
 
 have been evaluated in subjects with RA over the course of a 12-week 
period (28 subjects).  Repeated doses of up to 
 g 
 have been evaluated in 
subjects with cGVHD over a 52-week period (32 subjects).  Repeated doses of up to 
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 g 
 have been evaluated in subjects with SLE over a 12-week treatment 
period (25 subjects).   
Based upon the totality of available safety data through 26 April 2022, the benefit/risk 
profile of efavaleukin alfa is favorable.  Efavaleukin alfa has been well tolerated in clinical 
studies and has an acceptable safety profile.  Adverse drug reactions reported with 
efavaleukin alfa in these clinical studies include erythema, pruritus, exacerbation in 
subjects with RA, hypersensitivity, and injection site reaction.  Potential risks include 
cardiovascular, respiratory, hematopoietic, changes in leukocyte population, 
immunomodulation, immunogenicity, and cytokine release syndrome.  More information 
about the safety profile of efavaleukin alfa may be found in the latest version of the 
3;*89.,&947H874(-:7* 
The above benefit risk assessment supports the conduct of this phase 2 clinical trial in 
subjects with UC.  
2.3.1 
COVID-19 
Amgen closely monitors the Corona virus-19 (COVID-19) pandemic around the world.  
As part of this effort, Amgen performs a rigorous assessment, considering the study 
design, patient safety, public health risk, benefit-risk assessment, as well as the burden 
on country healthcare systems.  Decisions are made on a study-by-study and 
country-by-country basis to minimize risk to patients and avoid undue burden on 
healthcare facilities.   
Patients who display symptoms consistent with COVID-19 infections or who have tested 
positive for COVID-19 should contact the investigator to ensure appropriate care as well 
as documentation and management of study activities. 
Amgen considers that it is important to continue the proposed development of 
efavaleukin alfa in this study in order to advance potential therapy options for patients as 
rapidly as possible, while balancing this with appropriate measures to monitor and 
mitigate the potential impact of COVID-19. 
Subjects enrolled in this study are permitted to receive vaccinations for COVID-19 
except as described in exclusion criterion 224 and Section 6.1.6. 
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3. 
Objectives and Endpoints/Estimands 
 
UC = ulcerative colitis 
Objectives 
Endpoints 
Primary 
 
To evaluate the effect of 
efavaleukin alfa on induction of 
clinical remission 
 
Clinical remission at week 12 
Primary Estimand 
Variable:  Clinical remission at week 12 
Estimator:  Difference in clinical remission rates 
Population:  All subjects with moderately to severely active UC with inadequate 
response, loss of response, or intolerance to at least 1 of the following: conventional 
therapy, biologics, or targeted small molecules, who are randomized. 
Treatments:  Each efavaleukin alfa dose group and placebo.   
Intercurrent event C composite variable strategy:  Subjects will be considered as not 
meeting the endpoint if they meet any of the following criteria prior to the week 12 visit: 
 
Initiation of or change in protocol-prohibited medication or concomitant UC 
medication 
 
A colectomy (partial or total) or an ostomy 
 
Discontinuation of investigational product 
Secondary 
 
To evaluate the effect of 
efavaleukin alfa on induction of 
clinical response 
 
Clinical response at week 12 
 
To evaluate the effect of 
efavaleukin alfa on induction of 
endoscopic remission 
 
Endoscopic remission at week 12 
 
To evaluate the effect of 
efavaleukin alfa on induction of 
symptomatic remission 
 
Symptomatic remission at 
week 12 
 
To evaluate the effect of 
efavaleukin alfa as induction 
therapy on combined endoscopic 
and histologic remission 
 
Combined endoscopic remission 
and histologic remission of the 
colon tissue at week 12 
 
To evaluate the effect of 
efavaleukin alfa as induction 
therapy on change in histological 
score 
 
Change from baseline in 
histological score at week 12 as 
measured by Geboes score 
 
To evaluate the safety and 
tolerability of efavaleukin alfa 
 
Treatment-emergent adverse 
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Endpoint Definitions 
 
Clinical Remission 
 
Modified Mayo score 0 to 2 including rectal bleeding 
subscore of 0, a stool frequency subscore of 0 or 1, 
and an endoscopy subscore of 0 or 1 (modified so 
that 1 does not include friability) 
 
Clinical Response 
 
A decrease from baseline in the modified Mayo 
score of 
 2 points and at least 30 reduction from 
baseline, and a decrease in the rectal bleeding 
subscore of 
 1 or an absolute rectal bleeding 
subscore of 0 or 1 
 
Endoscopic remission 
 
Mayo endoscopy subscore of 0 or 1(modified so 
that a score of 1 does not include friability) 
 
Symptomatic remission 
 
Mayo stool frequency subscore of 0 or 1 and rectal 
bleeding subscore of 0 
 
Combined endoscopic 
and histologic remission 
 
Combined endoscopic remission (Mayo endoscopy 
subscore of 0 or 1) and histologic remission of the 
colon tissue (Geboes Score  2.0; no neutrophils in 
the epithelium crypts or lamina propria and no 
increase in eosinophils, no crypt destruction and no 
erosions, ulcerations or granulation tissue) 
 
Safety and tolerability 
 
Subject incidence of treatment-emergent adverse 
events (including treatment-emergent adverse 
events for clinically significant changes in laboratory 
parameters and vital signs) 
 
Phase 2 Induction Period 
Exploratory 
 
To explore the effect of 
efavaleukin alfa as induction 
therapy on total Mayo score, 
partial Mayo score and individual 
subscores 
 
Change from baseline in total 
Mayo score at week 12 
 
Change from baseline in partial 
Mayo score at each assessment 
through week 12 
 
Change in individual Mayo 
subscore at each assessment 
through week 12 
 
To explore the effect of 
efavaleukin alfa on induction of 
symptomatic and endoscopic 
remission without concomitant 
corticosteroid use 
 
Symptomatic remission at 
week 12 without concomitant 
corticosteroid use from baseline 
through week 12  
 
Endoscopic remission at week 12 
without concomitant corticosteroid 
use from baseline through 
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To explore the effect of 
efavaleukin alfa as induction 
therapy on calprotectin levels in 
fecal samples 
 
Change from baseline in fecal 
calprotectin at week 12 
 
To explore the effect of 
efavaleukin alfa as induction 
therapy on lactoferrin levels in 
fecal samples 
 
Change from baseline in fecal 
lactoferrin at week 12 
 
To explore the effect of 
efavaleukin alfa as induction 
therapy on CRP levels 
 
Change from baseline in CRP 
levels through week 12 
 
To explore the immunological 
effects (pharmacodynamics) of 
efavaleukin alfa 
 
Fold changes from baseline of 
Treg, CD4Tcon, CD8 T cells, 
and NK absolute cell counts 
(cells/L) after efavaleukin alfa 
administration 
 
To characterize the PK of 
efavaleukin alfa 
 
Trough and sparse postdose 
serum concentrations of 
efavaleukin alfa 
 
To explore efavaleukin alfa 
immunogenicity 
 
Anti-efavaleukin alfa antibodies 
and crossreactivity with IL-2 
 
Anti-efavaleukin alfa and anti-IL-2 
neutralizing antibodies 
 
To explore the effect of 
efavaleukin alfa as induction 
therapy on functioning and 
 
Change from baseline in social 
function and emotional function 
scores as measured by IBDQ at 
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health-related quality of life 
week 12 
 
Changes from baseline in IBDQ 
overall score at week 12 
 
To explore the effect of 
efavaleukin alfa as induction 
therapy on changes in quality of 
life 
 
Change from baseline in VAS 
scores as measured by the 
EQ-5D-5L at week 12 
 
To explore the effect of 
efavaleukin alfa as induction 
therapy on UC-related 
hospitalizations 
 
Incidence and duration of 
UC-related hospitalizations at 
week 12 
 
To explore the effect of 
efavaleukin alfa as induction 
therapy on colectomy or 
UC-related complications 
 
Colectomy for UC or UC-related 
complications at week 12 
CRP = C-reactive protein; EQ-5D-5L = EuroQol-5-Dimension 5 levels; IBDQ = Inflammatory Bowel Disease 
Questionnaire; IL-2 = interleukin-2; NK = natural killer; PK = pharmacokinetics; 
 
 UC = ulcerative colitis; 
; 
VAS = visual analogue scale 
Long-term Treatment Period 
Exploratory 
 
To explore the efficacy of 
long-term treatment with 
efavaleukin alfa 
 
Sustained clinical remission at 
week 12 and week 52 
 
Clinical remission at week 52 
 
Clinical response at week 52 
 
Endoscopic remission at week 52 
 
Corticosteroid-free clinical 
remission at week 52 in subjects 
receiving corticosteroids at 
randomization  
 
Combined endoscopic and 
histologic remission at week 52 
 
To explore the long-term safety of 
efavaleukin alfa 
 
Treatment-emergent adverse 
events 
 
To explore efavaleukin alfa 
immunogenicity during long-term 
treatment 
 
Anti-efavaleukin alfa antibodies 
and crossreactivity with IL-2 
 
Anti-efavaleukin alfa and anti-IL-2 
neutralizing antibodies 
 
To explore the effect of 
efavaleukin alfa long-term 
treatment on total Mayo score, 
partial Mayo score and individual 
subscores 
 
Change from baseline in total 
Mayo score at week 52 
 
Change from baseline in partial 
Mayo score at each assessment 
through week 52  
 
Change from baseline in individual 
Mayo subscore at each 
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assessment through week 52 
 
To explore effect of efavaleukin 
alfa long-term treatment on 
calprotectin levels in fecal 
samples 
 
Change from baseline in fecal 
calprotectin at week 52 
 
To explore the effect of 
efavaleukin alfa long-term 
treatment on functioning and 
health-related quality of life 
 
Change from baseline in social 
function and emotional function 
scores as measured by the IBDQ 
at week 52 
 
Change from baseline in IBDQ 
overall score at week 52 
 
To explore the effect of 
efavaleukin alfa long-term 
treatment on changes in quality of 
life 
 
Change from baseline in VAS 
scores as measured by the 
EQ-5D-5L at week 52 
EQ-5D-5L = EuroQol-5-Dimension 5 levels; IBDQ = Inflammatory Bowel Disease Questionnaire; 
IL-2 = interleukin-2; 
; UC = ulcerative colitis; 
; VAS = visual analogue scale. 
4. 
Study Design 
4.1 
Overall Design 
This phase 2 dose-finding study is a multicenter, randomized, double-blind, 
placebo-controlled, parallel-group, 12-week induction study of efavaleukin alfa in 
subjects with moderately to severely active UC who have failed at least 1 of the 
following: conventional therapy (eg, immunomodulators, corticosteroids), biologic 
therapy, or targeted small molecule (eg, JAK inhibitors).  This study will be used to 
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establish the efavaleukin alfa induction dose and maintenance dose/dosing regimens for 
continued development.  Subjects who complete the 12-week induction period will have 
the option to be treated in an exploratory long-term treatment period for up to 
40 additional weeks if in the opinion of the investigator they may benefit from continued 
treatment.  The primary analysis will occur after all subjects have completed the week 12 
visit or have early terminated.  All primary and secondary objectives will be evaluated at 
the primary analysis.  The objectives and endpoints for the study are defined in 
Section 3.  The overall study design is described by a study schema in Section 1.2 
(Figure 1-1). 
4.1.1 
Induction Period 
Approximately 240 subjects will be assigned in a 1:1:1:1 ratio to placebo or 1 of 
3 efavaleukin alfa dose parallel groups (n  60 per group) as follows: 
 
Placebo 
 
 
 g 
 
 
 g 
 
 
 g 
 
Randomization will be stratified by prior experience with at least 1 biologic or targeted 
small molecule (yes/no) and corticosteroid use at randomization (yes/no).  
Approximately 30 of enrolled subjects are allowed to be naïve to biologic or targeted 
small molecule therapy.  Screening may be closed for subjects naïve to biologic or 
targeted small molecule therapy, if based on current enrolled subjects and those in 
screening, it is anticipated that enrolment of subjects naïve to a biologic or targeted 
small molecule will be greater than 30% of the total planned enrolment.  Subjects in this 
clinic&1.3;*89.,&9.438-&11'*7*+*77*)94&8E8:'/*(98F479-*8&251*8.?*/:89.+.(&9.4n, 
see Section 9.2. 
Clinical remission and clinical response will be assessed at the end of the 12-week 
induction period by the modified Mayo score using centrally read endoscopy subscore 
(see Section 8.3.1).  Week 12 was selected as the time point for induction efficacy 
assessments based on available clinical data from a study of UC patients with low-dose 
IL-2 (Section 2.1).  For efavaleukin alfa, 12 weeks is predicted to allow sufficient duration 
of therapy with sustained Treg expansion to provide an optimal induction remission rate.  
Once a subject completes safety and efficacy assessments at week 12, they will have an 
option to be treated in an exploratory long-term treatment period, if in the opinion of the 
investigator, they would benefit from continued treatment (Section 4.1.2). 
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If a subject discontinues investigational product during the induction period, the subject 
will be encouraged to maintain the planned scheduled assessments through week 52 
(Table 1-3).   
If the subject discontinues the study completely prior to week 52, the subject should 
complete an early termination (ET) visit (ie, week 52 visit procedures) which must be 
scheduled to allow for 
 
  If a subject undergoes ET soon after having their screening or 
week 12 endoscopy, the need for an ET endoscopy should be discussed with the 
Amgen physician. 
Interim analyses will be performed to assess futility (Section 9.4.1.1). 
An independent Data Monitoring Committee (DMC) will oversee safety and overall 
conduct of the study (Section 11.3).  The first 2 DMC meetings will occur after the first 
20 subjects randomized have had the opportunity to complete the 
 and week 12 
visits.  Thereafter the DMC will plan to meet approximately every 3 months until Amgen 
is unblinded at the primary analysis.  After Amgen is unblinded, the DMC will plan to 
meet every 6 months.  Ad hoc meetings can be scheduled as needed.  The DMC will 
also review all available safety and efficacy data for interim analyses (see 
Section 9.4.1.1 for timepoints).  
4.1.2 
Long-term Treatment Period 
Subjects who complete the safety and efficacy evaluations at week 12, have not 
discontinued investigational product, and who in the opinion of the investigator may 
benefit from continued treatment, will have the option to continue treatment in an 
exploratory long-term treatment period.  The long-term treatment period will provide 
opportunity to explore the long-term safety and efficacy of continued treatment with 
efavaleukin alfa for up to 40 weeks (total of up to 52 weeks of treatment).  During the 
long-term treatment period, subjects will continue to receive their assigned blinded dose 
of investigational product (placebo or efavaleukin alfa) at the week 12 visit.  The 
exception will be placebo nonresponder subjects, who are defined as those randomized 
to placebo during the induction period and who failed to achieve clinical response at 
week 12.  These placebo nonresponder subjects will be assigned in a blinded manner to 
receive 
 g 
 dose during the long-term treatment period.  Treatment 
assignment during the long-term treatment period will be done by interactive response 
technology (IRT) based on the modified Mayo score using the locally read endoscopy 
subscore assigned by the investigator (refer to Section 6.1.1.2). 
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During the long-term treatment period, subjects will be assessed for worsening of 
disease activity, defined by a partial Mayo score of 
 4 with an increase from week 12 in 
rectal bleeding subscore to 
 2 and/or an increase from week 12 in stool frequency 
subscore to 
 2.  It is recommended that the investigator should determine whether a 
subject should discontinue investigational product based on worsening of disease 
activity, either based on the partial Mayo criteria above or their clinical judgement.  
Subjects who were nonresponders at week 12, and who have an inadequate response 
by 
 will be discontinued from further investigational product administration in 
long-term treatment period. 
Inadequate response is defined by failure to achieve a 2-point reduction and 25 
improvement in partial Mayo score compared to the partial Mayo score at screening (and 
a minimum partial Mayo score of 
 5 points) at 
 
Efficacy evaluations during the long-term treatment period will include the total and 
partial Mayo score, fecal calprotectin, and corticosteroid use.  The modified Mayo score 
(including endoscopy) and mucosal biopsies for histopathology will be assessed at the 
week 52/ early termination visit. 
If a subject discontinues investigational product prior to week 52, the subject will be 
encouraged to maintain the planned scheduled assessments through week 52 
(Table 1-3).   
If the subject discontinues the study completely prior to week 52, the subject should 
complete an early termination (ET) visit (ie, week 52 visit procedures) which must be 
scheduled to allow for 
 
  If a subject undergoes ET soon after having their week 12 
endoscopy, the need for an ET endoscopy should be discussed with the Amgen 
physician. 
Subjects who complete the week 52 endoscopy and who, in the opinion of the 
investigator, may benefit from continued treatment, will be assessed for eligibility to roll 
over into the Phase 2 Long Term Extension Study (20210210).  
4.1.3 
Safety Follow-up Period 
The safety follow-up period consists of a single safety follow-up visit.  
 
 
   
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4.2 
Patient Input into the Study Design 
Patient input was obtained for design of a study to treat UC.  Two patient panels were 
queried to obtain insights to optimize study design and decrease patient burden. 
4.3 
Justification for Dose 
4.3.1 
Justification for Investigational Product Dose 
In this study, subjects with moderately to severely active UC will be randomized to 
receive one of the following induction doses: 
 g 
 
 g 
 
 g 
 
or placebo 
  The planned induction doses were selected based on i) analyses of 
efavaleukin alfa pharmacokinetic (PK) and pharmacodynamic (PD) from completed and 
ongoing phase 1 studies to date ii) Treg data from a single arm open label study of low 
dose IL-2 in subjects with moderately to severely active UC (Allegretti et al, 2020)  iii) 
safety data from completed and ongoing studies. 
All planned doses have demonstrated acceptable safety in phase 1 studies (Please see 
3;*89.,&947H874(-:7* for further details).  In addition, clinical results from studies of UC 
patients treated with low dose IL-2 suggest that UC patients may benefit from treatment 
with efavaleukin alfa (Allegretti et al, 2020).  The highest proposed dose of 
 g 
 was evaluated in a phase 1b study of subjects with SLE and was found to have 
acceptable safety and tolerability. 
A subsequent dosing cohort of 
 g 
 was also found to have acceptable safety 
and tolerability but has not been included in phase 2 studies due to an apparent plateau 
in fold-expansion of T regulatory cells and low-level fold-increase in other IL-2C
responsive cells, although interpretation is limited due to small subject numbers.  As of 
26 April 2022, no deaths, life-threatening, or serious treatment emergent adverse events 
have been reported in these ongoing cohorts. 
 
.  The PD has 
demonstrated dose-dependent, selective Treg expansion that peaks at day 8 post-dose 
with no meaningful expansion of CD4 Tcon, CD8 Tcells and NK cells.  
 
 
 
 
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Based on exposure-Treg modeling of all available efavaleukin alfa phase 1 data, the 
 g 
 dose is predicted to yield an approximate 
 in Tregs from 
baseline (Inter-quartile range [IQR] range:  
); the 
 g 
 dose is predicted 
to yield an approximate 
 in Tregs from baseline (IQR range:  
 the 
 g 
 dose is predicted to yield an approximate 
 in Tregs number 
from baseline (IQR range:
). 
The doses 
 g 
 
 g 
 
 g 
 have been tested in the ongoing 
phase 1b study in subjects with SLE.  Observed Treg expansion aligned with ranges 
predicted by exposure-Treg modeling.  Peak Treg expansion at each dose was 
statistically differentiated from placebo and from each other dose.  There were no 
statistically significant differences in CD4 Tcon expansion between efavaleukin alfa at 
any dose and placebo.  The planned phase 2b doses are anticipated to test a 
differentiated range of Treg expansion in subjects with UC and will further inform our 
understanding of the target level of Treg expansion required for efficacy in this patient 
population. 
Efavaleukin alfa SLE phase 1b Treg data were compared with Treg/clinical response 
data from a published study of low dose IL-2 in subjects with moderately to severely 
active UC.  After 8 weeks of treatment, clinical response or remission was observed in 9 
of 15 (or 60%) subjects treated with an effective dose of low dose IL-2 (Allegretti et al, 
2020).  The ranges of peak Treg expansion observed at efavaleukin alfa doses of 
greater than or equal to 
 g in subjects with SLE are approximately comparable to 
peak blood Treg concentrations associated with clinical efficacy in subjects with UC 
treated with low dose IL-2 (Allegretti et al, 2020).  This comparison may be limited by 
significant methodological differences and the assumption that subjects with SLE and 
UC will provide similar PD responses. 
 dosing frequencies have been evaluated in 3 multiple-dose 
phase 1b studies and have been found to produce similar peak Treg expansion that was 
generally sustained over multiple doses.  However, comparison of trough Treg 
concentrations across dosing frequency was inconclusive because of limited 
 data 
and large inter-subject variability.  Once 
 dosing was selected for all doses 
in this phase 2b study because:  1) peak Treg concentrations are predicted to be similar 
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and sustained across multiple 
 and 
 dosing, and 2) 
 is predicted to yield 
blood Treg trough values approximately 2 weeks after dosing that remain well above 
baseline concentrations in the dose range proposed.  These predictions are consistent 
with observed Treg data from RA, SLE, and cGvHD phase 1b studies.  In addition, given 
the similarity in peaks and variability in 
 troughs, patient convenience was 
considered.  Therefore, a 
 regimen was determined to be the optimal frequency for 
efavaleukin alfa in Study 20170104 based on current data. 
The anticipated exposures for the planned doses are well below those that were 
observed at the NOAEL in the Good Laboratory Practice cynomolgus monkey toxicology 
studies, with maximum observed concentration (Cmax) and area under the concentration-
time curve (AUC) margins of 3 and 16.3, respectively, for the highest dose of 
 g 
  Please see 3;*89.,&947H874(-:7* for further details. 
4.4 
End of Study 
An individual subject is considered to have completed the study if they have remained 
on study for the entire treatment period (ie through the week 52 visit) and completed the 
 (if applicable, see Table 1-4).  The total study duration for an 
individual subject may be up to 61 weeks.  This includes up to a 35-day screening 
period, 12 weeks of induction treatment, up to 40 weeks of long-term treatment, and a 
The end of study date for the entire study is defined as the date when the last subject 
across all sites is assessed or receives an intervention for evaluation in the study (ie, last 
subject last visit), including any additional parts in the study (eg, long-term follow-up), as 
applicable. 
5. 
Study Population 
Investigators will be expected to maintain a screening log of all potential study 
candidates that includes limited information about the potential candidate (eg, date of 
screening). 
Eligibility criteria will be evaluated at the screening visit and at the day 1 visit prior to 
randomization. 
Before any study-specific activities/procedures, the appropriate written informed consent 
must be obtained (see Section 11.3). 
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Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions will not be provided. 
5.1 
Inclusion Criteria 
Subjects are eligible to be included in the study only if all of the following criteria apply: 
 
101 
Subject has provided informed consent prior to initiation of any study specific 
activities or procedures.   
102 
Age 
 18 years to  80 years at screening visit, except in South Korea where age 

 19 years to  80 years at screening visit. 
103 
Diagnosis of UC established 
 3 months prior to enrollment by clinical and 
endoscopic evidence and corroborated by a histopathology report.  If a 
histopathology report is not available at screening, then additional biopsies may 
be taken during the screening period for local histopathology analysis to 
corroborate. 
104 
Moderately to severely active UC as defined by a modified Mayo score of 5 to 9, 
with a centrally read endoscopy subscore 
 2. 
105 
Has documentation of 
 
A surveillance colonoscopy (performed according to local standard) within 
12 months of day 1 visit for subjects with pancolitis of  8 years duration, 
or subjects with left-sided colitis of  12 years duration, or subjects with 
primary sclerosing cholangitis. 
 
For all other subjects, up-to-date colorectal cancer surveillance 
(performed according to local standard).  At the discretion of the 
investigator, a colonoscopy (instead of a rectosigmoidoscopy) may be 
performed as the screening endoscopy for this study.  Subjects who do 
not have a colonoscopy report available in source documentation will 
have a colonoscopy instead of rectosigmoidoscopy performed as the 
screening endoscopy for the study 
106 
Subjects must have demonstrated inadequate response, loss of response, or 
intolerance to at least 1 conventional therapy, biologic therapy, or targeted small 
molecule therapy (ie, JAK-inhibitor). 
 
Conventional therapy failed subjects: 
- 
Corticosteroids (corticosteroid-refractory colitis, defined as signs 
and/or symptoms of active UC despite oral prednisone (or equivalent) 
at doses of at least 30 mg/day for a minimum of 2 weeks; or 
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 
- 
History of intolerance of corticosteroids (including, but not limited to, 
Cushing's syndrome, osteopenia/osteoporosis, hyperglycemia, or 
neuropsychiatric side-effects, including insomnia, associated with 
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- 
Immunomodulators: signs and/or symptoms of persistently active 
disease despite at least 3 months treatment with one of the following 
at locally approved doses: oral azathioprine (eg, 
 1.5 mg/kg/day) or 
6-mercaptopurine (eg, 
 0.75 mg/kg/day), or oral azathioprine or 
6-mercatopurine 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 
- 
History of intolerance to at least 1 immunomodulator (including but not 
limited to nausea/vomiting, abdominal pain, pancreatitis, liver function 
test abnormalities, and lymphopenia) and have neither failed nor 
demonstrated an intolerance to a biological medication (anti-TNF 
antibody, anti-integrin antibody, or IL-12/23 antagonists) that is 
indicated for the treatment of UC 
 
Biologic or targeted small molecule therapy failed subjects: those who 
demonstrated inadequate response or loss of response or intolerance to 
biologic therapy for UC (eg, anti-TNF antibodies or IL-12/23 antagonists, 
anti-integrin antibodies) or targeted small molecules (eg, JAK inhibitors or 
S1P modulators).  The therapy used to qualify the subject for entry into 
this category must be approved for the treatment of UC in the country of 
use, at the time of use.  Subjects must fulfil one of the following criteria: 
 
Inadequate response: signs and symptoms of persistently active 
disease despite induction treatment at the approved induction dosing 
that was indicated in the product label at the time of use 
 
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 quality as 
having failed or being intolerant to UC biological therapy or JAK 
inhibitor or S1P modulator) 
 
Intolerance:  history of intolerance to infliximab, adalimumab, 
golimumab, vedolizumab, ustekinumab, tofacitinib or other approved 
biologicals or JAK inhibitors or S1P modulators (including but not 
limited to infusion-related event, demyelination, congestive heart 
failure, or any other drug-related adverse event that led to a reduction 
in dose or discontinuation of the medication) 
107 
If receiving any of the following therapies, subjects must have stable dosage for 
the specified duration (refer to Section 11.9 for a summary of permitted 
medications): 
 
5-aminosalicylates (ASAs), stable dosage for 
 2 weeks prior to screening 
endoscopy 
 
Oral corticosteroids: prednisone  20 mg/day or its equivalent, stable dose for 

 2 weeks prior to screening endoscopy 
 
Budesonide:  extended-release tablets 9 mg/day [budesonide MMX], stable 
dose for 
 2 weeks prior to screening endoscopy 
 
Beclomethasone dipropionate: gastro-resistant prolonged-release tablet 5 
mg/day, stable dose for 
 2 weeks prior to screening endoscopy  
 
Conventional immunomodulators: azathioprine, 6-mercaptopurine, 
methotrexate, stable dosage for 
 12 weeks prior to screening endoscopy 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
Date:  21 August 2024 
Page 43 of 131 
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5.2 
Exclusion Criteria 
Subjects are excluded from the study if any of the following criteria apply: 
Disease Related 
201 
.&,348.84+74-3H8).8*&8*.3+1&22&947>'4<*1).8*&8*-unclassified 
(indeterminate colitis), microscopic colitis, ischemic colitis, or clinical findings 
8:,,*89.;*4+74-3Hs disease. 
202 
Disease limited to the rectum (ie, within 15 cm of the anal verge).   
203 
Evidence of toxic megacolon, fulminant colitis, intra-abdominal abscess, or 
stricture/stenosis within the small bowel or colon. 
204 
Previous bowel resection or intestinal or intra-abdominal surgery. 
 
Have had extensive surgery for UC (for example, subtotal colectomy), or are 
likely to require surgery for the treatment of UC during the study.  Subjects 
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 must occur prior to screening of 
such subjects. 
 
Have had any small bowel or colonic surgery within 6 months of day 1. 
 
Have had any nonintestinal intra-abdominal surgery within 3 months of day 1. 
205 
Adenoma and dysplasia exclusion criteria: 
 
Any current sporadic adenoma without dysplasia (adenomatous polyps 
occurring proximal to known areas of colitis) that has not been removed.  
Once completely removed, the subject is eligible for study. 
 
Dysplasia occurring in flat mucosa, sporadic adenomas containing dysplasia, 
and dysplasia-associated lesions or masses will be managed as follows: 
 
Any history or current evidence of high-grade dysplasia. 
 
Any history or current evidence of dysplasia occurring in flat mucosa.  
This includes histopathology reporting indefinite for dysplasia, low-grade 
dysplasia, and high-grade dysplasia. 
 
Any history or current evidence of a nonadenoma-like 
dysplasia-associated lesions or masses, with or without evidence of 
dysplasia. 
 
Any current sporadic adenoma containing dysplasia or any current 
adenoma-like dysplasia-associated lesions or masses that has not been 
removed.  Once completely removed, the patient is eligible for the study. 
206 
Stool positive for Clostridium difficile toxin at screening and other enteric 
pathogens including but not limited to ova, parasites, Campylobacter, salmonella, 
shigella, E coli 0157:H7, and Yersinia enterocolitica. 
207 
History or evidence of suicidal ideation (severity of 4 or 5) or any suicidal 
behavior based on an assessment with the Columbia Suicide Severity Rating 
Scale (C-SSRS) at screening. 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
Date:  21 August 2024 
Page 44 of 131 
CONFIDENTIAL 
 
Other Medical Conditions 
208 
Active infection (including chronic or localized infections) for which anti-infectives 
were indicated within 2 weeks prior to screening visit OR presence of serious 
infection, defined as requiring hospitalization or intravenous (IV) anti-infectives 
within 8 weeks prior to screening visit. 
209 
Active tuberculosis (TB) or latent tuberculosis with no documented past history of 
adequate treatment per local standard of care. 
210 
Positive test for TB during screening defined as: either a positive or 
indeterminate QuantiFERON-TB or T-spot test OR positive purified protein 
derivative (PPD) (
 5 mm of induration at 48 to 72 hours after test is placed). 
 
Subjects with a positive PPD and a history of Bacillus Calmette-Guérin 
vaccination are allowed to enroll with a negative QuantiFERON®-TB or 
T-Spot test and negative chest X-ray. 
 
Indeterminate QuantiFERON®-TB or T-spot test can be repeated once, 
based on investigator judgment.  Subjects can enroll if second result is 
negative.  Subjects with persistent indeterminate or positive test results must 
proceed as below. 
 
Subjects with a positive PPD test (without a history of Bacillus Calmette-
Guérin vaccination) or a positive or indeterminate QuantiFERON®-TB or 
T-Spot test (including repeated results when performed) are allowed to enroll 
if they meet ALL the following criteria at screening: 
 
no symptoms per tuberculosis worksheet provided by Amgen 
 
documented history of adequate TB treatment or prophylactic treatment 
for latent TB (completed per local standard of care prior to the start of 
investigational product) 
 
no known exposure to a case of active tuberculosis after most recent 
treatment/prophylaxis 
 
chest X-ray with no new radiographic findings suggestive of active TB (to 
be read by local facility) 
211 
Any history of malignancy with the following exceptions: 
 
Resolved non-melanoma skin cancers > 5 years prior to screening. 
 
Resolved cervical in situ carcinoma > 5 years prior to screening. 
212 
Presence of 1 or more significant concurrent medical conditions per the 
investigator judgement, including but not limited to the following: 
 
Poorly controlled diabetes or hypertension 
 
Chronic kidney disease stage IIIb, IV, or V 
 
Symptomatic heart failure (New York Heart Association class II, III or IV) 
 
Myocardial infarction or unstable angina pectoris within the past 12 months 
prior to day 1 
 
Severe chronic pulmonary disease requiring oxygen therapy 
 
Major chronic inflammatory disease or connective tissue disease other than 
UC (eg, rheumatoid arthritis) 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
Date:  21 August 2024 
Page 45 of 131 
CONFIDENTIAL 
 
213 
Positive for hepatitis B surface antigen (HBsAg); or positive for hepatitis B core 
antibody (HBcAb) or hepatitis B surface antibody (HBsAb) in the presence of 
detectable viral DNA in peripheral blood, assessed by polymerase chain reaction 
(PCR).  Subjects positive for HBcAb and/or HBsAb without history of prior 
vaccination and without detectable serum hepatitis B viral DNA by PCR are 
allowed to enroll, provided the subject undergoes monitoring of serum hepatitis B 
viral DNA by PCR at every 2 months during the treatment period and up to 
6 weeks after the end of treatment for the study.  Subjects with a history of 
hepatitis B vaccination without history of hepatitis B infection (ie, positive HBsAb, 
negative HBsAg, and negative HBcAb) are allowed to enroll. 
214 
Positive for hepatitis C antibody (HCAb) in the presence of detectable viral RNA 
in peripheral blood, assessed by PCR.  Subjects positive for HCAb without 
detectable viral RNA by PCR are allowed to enroll. 
215 
Known history of Human Immunodeficiency Virus (HIV) or positive HIV test at 
screening. 
216 
Inherited immunodeficiency syndrome. 
217 
Required systemic corticosteroid use for any indication other than UC.  The only 
exception is corticosteroids used for the treatment of adrenal insufficiency are 
allowed. 
218 
Have had a bone marrow or solid organ transplantation. 
219 
Have had extra-abdominal surgery without full recovery prior to screening. 
Prior/Concomitant Therapy (refer to Section 11.8 for a summary of prohibited 
medications): 
220 
Currently receiving or had treatment within 12 months prior to screening with 
T cell depleting agents (eg, antithymocyte globulin, Campath). 
221 
Currently receiving or had treatment with recombinant IL-2 (eg, Proleukin). 
222 
Corticosteroid enemas, corticosteroid suppositories, a course of 
intravenous corticosteroids or intramuscular corticosteroids, or oral budesonide 
standard formulation within 2 weeks prior to screening endoscopy. 
223 
5-ASA enemas or 5-ASA suppositories within 2 weeks prior to screening 
endoscopy. 
224 
Subjects who have received live vaccines within 5 weeks prior to screening, or 
plan to receive live vaccines during the treatment period and up to 6 weeks after 
the last dose of investigational product in the study. 
225 
Has received any of the following prescribed medication or therapy within the 
specified time period: 
 
Anti-TNF antibodies (eg, infliximab, adalimumab, golimumab)  8 weeks prior 
to screening endoscopy 
 
Anti-integrin antibodies (eg, vedolizumab) < 8 weeks prior to screening 
endoscopy 
 
IL-12/23 antagonist (eg, ustekinumab) < 8 weeks prior to screening 
endoscopy 
 
JAK inhibitors (eg, tofacitinib) < 4 weeks prior to screening endoscopy 
 
S1P modulators (eg, ozanimod) II<**0857.47948(7**3.3,*3)48(45>. 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
Date:  21 August 2024 
Page 46 of 131 
CONFIDENTIAL 
 
 
Any other commercially approved biologic agent or targeted small molecule 
 8 weeks prior to screening endoscopy or < 5 half-lives prior to screening 
endoscopy, whichever is longer 
 
Immunomodulatory medications oral cyclosporine, IV cyclosporine, 
tacrolimus, sirolimus, mycophenolate mofetil, thalidomide < 4 weeks prior to 
screening endoscopy 
 
Any investigational biologic therapy within 8 weeks prior to screening 
endoscopy or < 5 half-lives prior to screening endoscopy, whichever is longer 
 
Have used apheresis (eg, Adacolumn apheresis) < 2 weeks prior to 
screening endoscopy 
Diagnostic Assessments 
226 
Abnormal laboratory results at screening: 
 
aspartate aminotransferase (AST) or alanine amino transferase (ALT) at 
screening > 1.5 X upper limit of normal (ULN) 
 
serum total bilirubin (TBL) 
 1.5 mg/dL (
 26 mol/L) 
 
Subjects with established diagnosis of Gi1'*79H88>3)742*&7*&114<*).+
TBL  3X ULN (source documentation demonstrating unconjugated 
hyperbilirubinemia and no evidence of hemolysis required). 
 
hemoglobin  8.5 g/dL ( 85 g/L) 
 
platelet count < 100 000/mm3 (< 100 x 109/L) 
 
white blood cell count  3000 cells/mm3 ( 3.0 x 109/L) 
 
absolute neutrophil count (ANC) < 1500/mm3 ( 1.5 x 109/L) 
227 
Any other laboratory abnormality, which, in the opinion of the investigator, poses 
a safety risk, will prevent the subject from completing the study, will interfere with 
the interpretation of the study results, or might cause the study to be detrimental 
to the subject. 
Prior/Concurrent Clinical Study Experience 
228 
Currently receiving treatment in another investigational device or drug study 
229 
Ending treatment with an investigational drug or investigational device less than 
3 months or 5 half-lives from the last dose of the investigational drug (whichever 
is longer) at screening. 
Other Exclusions 
230 
Female subject is pregnant or breastfeeding or planning to become pregnant or 
breastfeed during study and for an additional 6 weeks after the last dose of 
investigational product.  Subjects who suspend breastfeeding prior to starting 
treatment with the study drug and do not intend to resume breastfeeding within 
6 weeks after receiving the last dose of investigational product can be enrolled. 
231 
Females of child-bearing potential (Section 11.5) with a positive pregnancy test 
(assessed by a serum pregnancy test at screening and a urine pregnancy test at 
day 1) 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
Date:  21 August 2024 
Page 47 of 131 
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232 
Female subject of childbearing potential unwilling to use at least 1 protocol 
specified method of contraception (Section 11.5) during treatment and for an 
additional 6 weeks after receiving the last dose of investigational product 
233 
Subject has known sensitivity to any of the products to be administered during 
dosing. 
234 
Subject likely to not be available to complete all protocol-required study visits or 
procedures, and/or to comply with all required study procedures (eg, Clinical 
Outcom*88*882*398949-*'*894+9-*8:'/*(9&3).3;*89.,&947H8034<1*),* 
235 
History or evidence of any other clinically significant disorder, condition or 
disease (with the exception of those outlined above) that, in the opinion of the 
investigator or Amgen physician, if consulted, would pose a risk to subject safety 
or interfere with the study evaluation, procedures or completion. 
236 
Current history of alcohol dependence and/or drug abuse within 1 year of day 1. 
237 
Female subjects of reproductive potential must agree not to donate eggs 
during the study and for 6 weeks after receiving the last dose of 
investigational product. 
5.3 
Subject Enrollment 
Before subjects begin participation in any study-specific activities/procedures, Amgen 
requires a copy of the s.9*H8written institutional review board/independent ethics 
committee (IRB/IEC) approval of the protocol, informed consent form (ICF), and all other 
subject information and/or recruitment material, as applicable (see Section 11.3). 
The subject must personally sign and date the IRB/IEC and Amgen approved informed 
consent before commencement of study-specific procedures.   
A subject is considered enrolled when the investigator decides that the subject has met 
all eligibility criteria.  The investigator is to document this decision and date, in the 
8:'/*(9H82*).(&17*(47)&3).3439-*":'/*(9374112*39(&8*7*5479+472! 
Each subject who enters into the screening period for the study (defined as the point at 
which the subject signs the ICF) receives a unique subject identification number before 
any study-related activities/procedures are performed.  The subject identification number 
will be assigned by the IRT system.  This number will be used to identify the subject 
throughout the clinical study and must be used on all study documentation related to that 
subject. 
The subject identification number must remain constant throughout the entire clinical 
study; it must not be changed after initial assignment, including if a subject is 
rescreened.  This number will not be the same as the randomization numbers assigned 
for the study. 
Sites that do not enroll subjects within 6 months of site initiation may be closed. 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
Date:  21 August 2024 
Page 48 of 131 
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5.4 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study 
but are not subsequently enrolled in the study.  A minimal set of screen failure 
information will be collected that includes demography, screen failure details, eligibility 
criteria, and any serious adverse events.  Refer to Section 8.1.1 for rescreen 
procedures. 
5.5 
Eligibility Requirements for Progression to Long-term Treatment 
Subjects enrolled in the induction period who complete the week 12 visit and who have 
not discontinued investigational product will have the option to continue to be treated in 
the exploratory long-term treatment period if in the opinion of the investigator they would 
benefit from further treatment. 
6. 
Study Intervention 
Study intervention is defined as any investigational product(s), non-investigational 
product(s), placebo, combination product(s), or medical device(s) intended to be 
administered to a study subject according to the study protocol. 
Note that according to local regulations in several countries, investigational product(s) 
described in Section 6.1.1 are referred to as investigational medicinal product(s) and 
non-investigational product(s) and other protocol-required therapies are referred to as 
non-investigational medicinal product(s)/auxiliary medicinal product(s). 
A summary of the dosing and administration of each treatment is shown below. 
6.1 
Study Interventions Administered 
6.1.1 
Investigational Products 
Efavaleukin alfa and placebo will be manufactured and packaged by Amgen Inc. and 
distributed using Amgen clinical study drug distribution procedures. 
Efavaleukin alfa or placebo will be administered by SC injection in the abdomen, thigh or 
upper arm by authorized site personnel on day 1.  A physician must be available at the 
time of the first dose of the investigational product administration. 
The dose of investigational product must be given within the window of time specified for 
the scheduled time point (see Schedule of Activities Table 1-1, Table 1-2, and Table 1-3) 
and any 2 consecutive doses of investigational product must be at least 7 days apart.  If 
that window is missed, that dose will not be administered, and the next dose will be 
administered at the next scheduled dosing date.  Note: For subjects continuing in the 
long-term treatment period (Section 6.1.1.2), investigational product administration at 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
Date:  21 August 2024 
Page 49 of 131 
CONFIDENTIAL 
 
week 12 has a dosing window up to  3 days after the week 12 visit to allow for dosing 
on a separate day from the endoscopy. 
 
 
Subjects who will continue to receive 
investigational product in the long-term treatment period 
 
 
For each vial, the total volume of preparation, quantity administered, start date, start 
time, and box 3:2'*74+*+&;&1*:0.3&1+&51&(*'4&7*94'*7*(47)*)43*&(-8:'/*(9H8
electronic case report form (eCRF). 
6.1.1.1 
Dose Administration and Schedule in the Induction Period 
The placebo and efavaleukin alfa doses will be administered by SC injection 
 
starting on day 1 through week 12.  The following treatment groups are planned: 
 
Placebo 
 
 
Efavaleukin alfa 
 g 
 
 
Efavaleukin alfa 
 g 
 
 
Efavaleukin alfa 
 g 
 
6.1.1.2 
Dose Administration and Schedule in the Long-term Treatment 
Period 
Subjects will continue to receive their assigned blinded dose of investigational product 
(placebo or efavaleukin alfa) beginning at the week 12 visit.  The exception will be 
placebo nonresponder subjects, who are defined as those randomized to placebo during 
the induction period and failed to achieve clinical response at week 12.  These placebo 
nonresponder subjects will be assigned in a blinded manner to receive 
 g 
 
dose during the long-term treatment period (Table 6-1).  For the purposes of treatment 
assignment into the long-term treatment period, clinical response is defined as a 
decrease from baseline in the modified Mayo score (using the endoscopic subscore 
assigned by the investigator) of 
 2 points and at least 30% reduction from baseline, and 
a decrease in the rectal bleeding subscore of 
 1 or an absolute rectal bleeding 
subscore of 0 or 1. 
Table 6-1.  Investigational Product Administration:  Long-term Treatment Period 
Investigational Product Administration 
Induction Period 
Long-term treatment period 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

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Page 50 of 131 
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Day 1 to Week 12 
Week 12 up to Week 52 or Early Termination 
Placebo 
 respondera, d 
Placebo 
 
Placebo 
 nonresponderb, d 
 g 
 
 g 
 d 
 g 
 
 g 
 d 
 g 
 
 g 
 d 
 g 
 
a A placebo responder subject is one who achieved clinical response at week 12. 
b A placebo nonresponder subject is one who did not achieve clinical response at week 12. 
c Subjects randomized to efavaleukin alfa will remain on the same dose through the long-term treatment 
period and includes responders and nonresponders. 
d Clinical response for the purpose of treatment assignment in the exploratory long-term treatment period will 
be assessed using the modified Mayo score and the endoscopic subscore assigned by the investigator. 
Subjects who were nonresponders at week 12, and who have an inadequate response 
by week
 will be discontinued from further investigational product administration in 
long-term treatment period (Section 4.1.2). 
6.1.2 
Medical Devices 
No investigational medical devices will be used in the study. 
Non-investigational medical devices may be used in the conduct of this study as part of 
standard care. 
Non-Amgen non-investigational medical devices (eg, syringes, sterile needles), that are 
commercially available are not usually provided or reimbursed by Amgen (except, for 
example, if required by local regulation).  The investigator will be responsible for 
obtaining supplies of these devices. 
6.1.3 
Other Protocol-required Therapies 
All other protocol-required therapies that are commercially available are not provided or 
reimbursed by Amgen (except if required by local regulation).  The investigator will be 
responsible for obtaining supplies of these protocol-required therapies. 
Concomitant medications are described in Section 6.7.2. 
6.1.4 
Other Intervention Procedures 
6.1.4.1 
Home Health Care Visits 
Section 6.1.4.1 is not applicable for participating sites in Bulgaria. 
If permitted by local regulations, the investigator may utilize a qualified home health care 
service provider, approved by sponsor, for collection of PK, biomarker samples and 
electrocardiogram (ECG) on visits without a scheduled administration of investigational 
CCI
CCI
CC
ICCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CC
ICCI
CCI
CCI
CCI
CCI
CCI
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Page 51 of 131 
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product.  In addition to PK, biomarker sample, and ECG collection, safety and 
concomitant medications data collection will be conducted. 
Home health care staff must be included on the study delegation log (authorized by the 
investigator) before any study-related tasks to be conducted by each home health care 
provider are started.  In addition, study-specific training including requirements for 
recording source documentation for the home health care provider, must be completed 
before they conduct any study-related tasks. 
Following home health care visits, all the information collected will be documented on 
the home health care services visit worksheet and provided to the investigator. 
A comprehensive list of all home health care services, as well as mandatory procedural 
and data collection requirements, will be separately provided in a home health care 
manual. 
6.1.5 
Product Complaints 
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 drug, combination product, or device after it is released for distribution 
to market or clinic by either (1) Amgen or (2) distributors or partners for whom Amgen 
manufactures the material.  This includes all components distributed with the drug, such 
as packaging drug containers, delivery systems, labeling, and inserts. 
This includes efavaleukin alfa/placebo provisioned and/or repackaged/modified by 
Amgen. 
Any product complaint(s) associated with efavaleukin alfa/placebo supplied by Amgen 
are to be reported 
6.1.6 
Excluded Treatments, Medical Devices, and/or Procedures During 
Study Period 
The following medications are not allowed at any time during the study: 
 
Any other investigational therapies or device 
 
T cell depleting agents (eg, antithymocyte globulin, Campath) 
 
Recombinant IL-2 (eg, Proleukin) 
 
Other immunomodulatory agents (including but not limited to cyclosporine, 
mycophenolate mofetil, tacrolimus, sirolimus) 
The following medications are prohibited unless the subject has stopped 
investigational product permanently: 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
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Page 52 of 131 
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Commercially available biologic agents (eg, vedolizumab, ustekinumab, antiTNFs 
[infliximab, adalimumab, or golimumab]) or biosimilars to these agents 
 
Targeted small molecules (eg, S1P modulators or JAK inhibitors) 
 
IV or intramuscular corticosteroids 
 
Live vaccines (prohibited up to 6 weeks after the last dose of investigational product 
in the study) 
 
Steroid or aminosalicylate based enemas 
6.2 
Dose Modification 
6.2.1 
Dose Treatment Group Study Escalation/De-escalation and Stopping 
Rules 
No dose group or cohort escalations are included in this study. 
6.2.2 
Dosage Adjustments, Delays, Rules for Withholding or Restarting, 
Permanent Discontinuation 
6.2.2.1 
Amgen Investigational Product:  Efavaleukin Alfa 
No dosage adjustments will be allowed during the study.  Subjects will be permanently 
discontinued from investigational product if they initiate excluded treatments as 
described in Section 6.1.6 at any time during the study. 
Refer to Section 7 for handling permanent discontinuation of investigational product. 
6.2.3 
Hepatotoxicity Stopping and Rechallenge Rules 
Refer to Section 11.7 for details regarding drug-induced liver injury guidelines, as 
specified in the Guidance for Industry Drug-Induced Liver Injury:  Premarketing Clinical 
Evaluation, July 2009. 
6.3 
Preparation/Handling/Storage/Accountability 
Both efavaleukin alfa and placebo are liquid formulations presented in highly similar 
glass vials and stored in the same manner.  Detailed information regarding the storage, 
preparation, and administration of investigational product will be provided separately. 
Guidance and information on drug accountability for the investigational products will be 
provided to the site. 
6.4 
Measures to Minimize Bias:  Randomization and Blinding 
6.4.1 
Method of Treatment Assignment 
6.4.1.1 
Subject Randomization 
At day 1, subjects will be randomized in a 1:1:1:1 ratio to placebo or 1 of the 
3 efavaleukin alfa dose parallel groups in a double-blind manner.  The randomization will 
be stratified by prior experience with at least 1 biologic or targeted small molecule 
(yes/no) and corticosteroid use at randomization (yes/no). 

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The randomization will be performed by IRT. 
#-*7&3)42.?&9.43)&9*.894'*)4(:2*39*).39-*8:'/*(9H82*).(&17*(47)&3)on the 
Subject Enrollment CRF (via IRT).  
During the long-term treatment period, subjects will be assigned to receive the same 
blinded treatment as received during the induction period, except for placebo 
nonresponder subjects who will be assigned to receive efavaleukin alfa (Table 6-1).  The 
treatment assignment will be performed by IRT. 
6.4.2 
Blinding 
This is a double-blind study.  Treatment assignment will be blinded to all subjects, site 
personnel, and Amgen as described below until all subjects have had the opportunity to 
complete the week 12 visit and the primary analysis has been completed. 
6.4.2.1 
Site Personnel Access to Individual Treatment Assignments 
8:'/*(9H897*&92*39&88.,32*39.8 to only be unblinded by the investigator when 
knowledge of the treatment is essential for the further management of the subject on this 
study or may potentially impact the safety of the subject.  Unblinding at the study site for 
any other reason will be considered a protocol deviation.  It is encouraged that the 
Amgen Trial Manager be notified before the blind is broken unless the investigator 
believes that identification of the study treatment is required for a medical emergency.  If 
this is not possible, the Amgen Trial Manager must be notified within 24 hours after 
breaking the blind.  The date and reason that the blind was broken must be recorded in 
the source documentation.  The unblinding of treatment assignment will be performed 
via IRT. 
6.4.2.2 
Access to Individual Subject Treatment Assignments by Amgen or 
Designees 
Blinded individuals will not have access to unblinded information until the study is 
formally unblinded.  Unblinding and potentially unblinding information is not to be 
distributed to the study team, investigators or subjects prior to the study being formally 
unblinded (eg, the formal unblinding may occur at the final analysis rather than during 
the primary analysis) except as specified (eg, Section 6.4.2.1). 
6.5 
Treatment Compliance 
When subjects are dosed at the site, they will receive investigational product directly 
from the investigator or designee, under medical supervision.  The date and time of each 

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dose administered in the clinic will be recorded in the source documents and recorded in 
the eCRF. 
6.6 
Treatment of Overdose 
The effects of overdose of this product are not known; therefore, no known treatment of 
overdose. 
6.7 
Prior and Concomitant Treatment 
6.7.1 
Prior Treatment 
Prior therapies that were being taken from 5 years of enrollment through the date of 
randomization should be collected.  Therapy name, dose, unit, frequency, start date, and 
stop date should be collected.   
6.7.2 
Concomitant Treatment 
Throughout the study, investigators may prescribe any concomitant medications or 
treatments deemed necessary to provide adequate supportive care except for those 
listed in Section 6.1.6 (summarized in Section 11.8). 
Concomitant therapies are to be collected from randomization through the end of study.  
For concomitant therapies being taken for UC, collect therapy name, indication, dose, 
unit, frequency, start date, stop date and reason for stopping.  For all other concomitant 
therapies, collect therapy name, indication, dose, unit, frequency, start date, and stop 
date. 
6.7.2.1 
Induction Period 
The following treatments for UC may not be initiated or have dose increased through 
end of the induction period (Section 5.1): 
 
Oral 5-ASA compounds (eg, sulfasalazine, mesalamine) 
 
Immunomodulators (azathioprine, 6-mercaptopurine, methotrexate) 
 
Oral corticosteroids including budesonide MMX or beclomethasone dipropionate 
(gastro-resistant prolonged-release tablet)  
Subjects who are receiving any of these treatments for UC at day 1 must keep their 
prescribed dosage stable throughout the induction period and the therapy can only be 
discontinued or reduced in dose if in the i3;*89.,&947H8(1.3.(&1/:),2*39.9.87*6:.7*)
because of toxicity or other medical necessity; even if the toxicity resolves, the therapy 
must not be restarted. 

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6.7.2.2 
Long-term Treatment Period 
The following UC-specific medical therapies must not be initiated or have the dose 
increased during the long-term treatment period: 
6.7.2.2.1 
Oral 5-ASA Compounds 
Oral 5-ASA therapy may not be initiated during long-term treatment period (stable dose 
is encouraged). 
6.7.2.2.2 
Immunomodulators 
Immunomodulators (6-mercaptopurine, azathioprine, or methotrexate): Subjects who 
were receiving any of these medical therapies for UC at the time of entry into the 
long-term treatment period and do not experience disease worsening must keep their 
prescribed dosage stable through completion of the long-term treatment visits unless in 
9-*.3;*89.,&947H8(1.3.(&1/:),2*399-*8*7*6:.7*).8(439.3:&9.4347)48*7*):(9.43
because of toxicity or other medical necessity; even if the toxicity resolves, the therapy 
must not be restarted. 
6.7.2.2.3 
Corticosteroids 
For subjects in clinical response or clinical remission (as assessed at week 12 by the 
modified Mayo score using locally read endoscopy subscore), who are receiving oral 
corticosteroids on entry into the long-term treatment period, the investigator must begin 
tapering the daily dose of corticosteroids at the week 12 visit. 
Recommended tapering schedule is as follows: 
 
For prednisone at doses > 10 mg/day (or equivalent), the dose should be 
reduced at a rate of 5 mg per week until a 10 mg/day dose is reached. 
 
4757*)3.843*&9)48*8A2,)&>47*6:.;&1*394743(*&2,)&>)48*
(or equivalent) is achieved by tapering, the dose should be reduced at a rate of 
2.5 mg/week until discontinuation. 
 
For budesonide MMX, the dose should be tapered at a rate of 3 mg every 3 
weeks until discontinuation. 
 
For beclomethasone dipropionate (gastro-resistant prolonged-release tablet), the 
dose should be tapered to 5 mg every other day for 4 weeks and then 
discontinued. 

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7. 
Discontinuation of Study Treatment and Subject 
Discontinuation/Withdrawal 
Subjects have the right to withdraw from investigational product and/or other 
protocol-required therapies, protocol procedures, or the study as a whole at any time 
and for any reason without prejudice to their future medical care by the physician or at 
the institution. 
The investigator and/or sponsor can decide to withdraw a subject(s) from investigational 
product, device, and/or other protocol-required therapies, protocol procedures, or the 
study as a whole at any time prior to study completion for the reasons listed below. 
7.1 
Discontinuation of Study Treatment 
Subjects (or a legally authorized representative) can decline to continue receiving 
investigational product and/or other protocol-required therapies and/or procedures at any 
time during the study but continue participation in the study.  If this occurs, the 
investigator is to discuss with the subject the appropriate processes for discontinuation 
from investigational product or other protocol-required therapies and must discuss with 
the subject the possibilities for continuation of the Schedule of Activities (see Table 1-1, 
Table 1-2, Table 1-3, and Table 1-4) including different options of follow-up (eg, in 
person, by phone/mail, through family/friends, in correspondence/communication with 
other treating physicians, from the review of medical records) and collection of data, 
.3(1:).3,*3)54.398&);*78**;*398&3)2:89)4(:2*399-.8)*(.8.43.39-*8:'/*(9H8
medical records.  Subjects who have discontinued investigational product and/or other 
protocol-required therapies and/or procedures should not be automatically removed from 
the study.  Whenever safe and feasible, it is imperative that subjects remain on-study to 
ensure safety surveillance and/or collection of outcome data.   
Reasons for early removal from protocol-required investigational product(s) may include 
any of the following: 
 
Decision by Sponsor 
 
Lost to follow-up 
 
Death 
 
Adverse event 
 
Subject request 
 
Ineligibility determined 
 
Protocol deviation 
 
Non-compliance 

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Pregnancy 
 
Requirement for alternative therapy 
 
Protocol-specified criteria: 
 
A colectomy (partial or total) or an ostomy 
 
Inadequate response per the partial Mayo score at 
 (for week 12 
nonresponders only) (see Section 4.1.2) 
 
Disease-worsening per the partial Mayo score during the long-term treatment 
period (see Section 4.1.2) 
7.2 
Subject Discontinuation/Withdrawal from the Study 
Withdrawal of consent for a study means that the subject does not wish to receive 
further protocol-required therapies or procedures, and the subject does not wish to or is 
unable to continue further study participation.  Subject data up to withdrawal of consent 
will be included in the analysis of the study, and where permitted, publicly available data 
can be included after withdrawal of consent.  The investigator is to discuss with the 
subject appropriate procedures for withdrawal from the study and must document the 
8:'/*(9H8)*(.8.4394<.9-)7&<.39-*8:'/*(9H82*).(&17*(47)8  Subjects who are 
withdrawn or removed from treatment or the study will not be replaced. 
If a subject withdraws from the study, they may request destruction of any samples 
taken and not tested, and the investigator must notify Amgen accordingly (see 
Section 11.6 for further details).  Refer to the Schedule of Activities (Table 1-2, 
Table 1-3, and Table 1-4) for data to be collected at the time of study discontinuation 
and follow-up and for any further evaluations that need to be completed. 
7.2.1 
Reasons for Removal from Study 
Reasons for removal of a subject from the study are: 
 
Decision by sponsor 
 
Withdrawal of consent from study 
 
Death 
 
Lost to follow-up 
7.3 
Lost to Follow-up 
A subject will be considered lost to follow-up if they repeatedly fail to return for 
scheduled visits and are unable to be contacted by the study site. 
The following actions must be taken if a subject fails to return to the clinic for a required 
study visit: 
 
The site must attempt to contact the subject and reschedule the missed visit as soon 
as possible and counsel the subject on the importance of maintaining the assigned 
CCI

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visit schedule and ascertain whether or not the subject wishes to and/or is able to 
continue in the study. 
 
In cases in which the subject is deemed lost to follow-up, the investigator or 
designee must make every effort to regain contact with the subject (where possible, 

9*1*5-43*(&118&3).+3*(*88&7>&(*79.+.*)1*99*7949-*8:'/*(9H81&89034<3
mailing address or local equivalent methods).  These contact attempts are to be 
documented in the subjec9H82*).(&17*(47) 
 
If the subject continues to be unreachable, they will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up. 
 
For subjects who are lost to follow-up, the investigator should search publicly 
available records where permitted to ascertain survival status.  This ensures that the 
data set(s) produced as an outcome of the study is/are as comprehensive as 
possible. 
8. 
Study Assessments and Procedures 
Study procedures and their time points are summarized in the Schedule of Activities 
(Table 1-1, Table 1-2, Table 1-3, and Table 1-4). 
If an enrolled subject is subsequently determined to be ineligible for the study, this must 
be discussed with the sponsor immediately upon occurrence or awareness to determine 
if the subject is to continue or discontinue study treatment. 
Adherence to the study design requirements, including those specified in the Schedule 
of Activities, is essential and required for study conduct. 
8.1 
General Study Periods 
8.1.1 
Screening, Enrollment and/or Randomization 
Visit assessments for screening, enrollment, randomization, and day 1 dose 
administration will occur per the Schedule of Activities (Table 1-1). 
Informed consent must be obtained before completing any screening procedure or 
discontinuation of standard therapy for any disallowed therapy.  After the subject has 
signed the ICF, the site will register the subject in the IRT and screen the subject in 
order to assess eligibility for participation.  The screening window is up to 35 days prior 
to first dose of investigational product. 
All screening evaluations must be completed and reviewed to confirm that potential 
subjects meet all eligibility criteria.  The investigator will maintain a screening log to 
record details of all subjects screened and to confirm eligibility or record reasons for 
screening failure, (see Section 5.4) as applicable. 
A subject must be in screening for at least 14 days prior to day 1 to enable a minimum of 
7 days of Mayo daily symptom diary collection prior to the screening endoscopy and to 

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enable results from the central reader assessment of the endoscopy to be received prior 
to the day 1 visit.  Stool frequency and rectal bleeding Mayo subscore calculation, 
laboratory results from blood collection, stool collection, and urinalysis results must have 
been received and confirmed eligible prior to subject proceeding to screening 
endoscopy. 
Mayo daily symptom diaries will be provided to each subject to record stool frequency 
and episodes of rectal bleeding.  The daily diaries will be completed from screening and 
will be used to calculate the stool frequency and rectal bleeding Mayo subscores 
(Section 8.3.194&88*889-*8:'/*(9H8*1.,.'.1.9>+47+:79-*78(7**3.3,&3)9497&.39-*
subject on the use of the daily diary (Section 8.3.1.1).  Subjects with a combined stool 
frequency and rectal bleeding subscore 
 2 (using the average of the 3 most recent days 
in the 7 days prior to initiation of bowel preparation for the screening endoscopy) can 
proceed with endoscopy (Section 8.3.1.2).  Subjects who do not have an up-to-date 
colorectal cancer surveillance colonoscopy in source document will have a colonoscopy 
instead of a rectosigmoidoscopy at screening as per inclusion criteria 105. 
The following laboratory parameters may be retested twice during the 35-day screening 
period: hematology, chemistry, urine analysis, stool samples for C. difficile and other 
enteric pathogens, indeterminate interferon gamma release assay for TB.  Under special 
circumstances the endoscopy may be repeated when, for example there is poor 
visualization of the enteric mucosa due to poor bowel preparation or because of 
technical issues with video recording equipment. 
At the day 1 visit, if the subject meets all eligibility criteria, they are subsequently 
enrolled and randomized to a treatment regimen. 
If a subject has not met all eligibility criteria at the end of the screening period and/or at 
the day 1 visit, the subject will be registered in IRT as a screen failure.  Screen fail 
subjects may be eligible for re-screening 2 times.  Subjects that are positive for HBsAg 
or positive for hepatitis C antibody as per exclusion criteria (213 and 214) or positive for 
HIV (exclusion criterion 215) will not be allowed to re-screen. 
Rescreen subjects must first be registered as screen failures in IRT and subsequently 
registered as rescreens.  Once the subject is registered as rescreened, a new 35-day 
screening window will begin.  Subjects will retain the same subject identification number 
assigned at the original screening.  

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If the rescreening period begins more than 35 days after the most recent signed 
informed consent form, then a new informed consent form must be signed. 
Eligible screening assessments from previous screening periods may be used if the 
assessment was performed within 35 days prior to randomization with the following 
exceptions and clarifications: 
 
Tuberculosis screening tests (QuantiFERON-TB, T-spot test OR positive PPD), 
serologies for hepatitis B virus, hepatitis C virus and HIV, provided that the 
rescreening occurs  12 2439-84+8(7**3.3,;.8.9&3)9-*7*.8345&9.*39H8
medical/epidemiological history suggestive of infection or recent exposure in cases 
of infection. 
 
If subject had received a course of antibiotics for C difficile toxin or another enteric 
pathogen, then subject must have discontinued antibiotic treatment for C difficile or 
other enteric pathogen at least 30 days prior to rescreening and testing for C difficile 
toxin or other enteric pathogens must be repeated.  It is recommended that local 
testing for C difficile toxin and other pathogens occur before rescreening to confirm 
negative status. 
8.1.2 
Induction Period 
Visits during the induction period will occur per the Schedule of Activities (Table 1-2).  
On-study visits must be completed within 	 5 days.  The date of the first dose of 
investigational product is defined as day 1.  All subsequent doses and study visits will be 
scheduled based on the day 1 date.  All patient reported outcomes (PROs) must be 
completed before any other study procedures for each visit.  The investigational product 
is to be administered following the completion of all other study-required procedures for 
each visit. 
8.1.3 
Long-term Treatment Period 
Visits during the exploratory long-term treatment period will occur per the Schedule of 
Activities (Table 1-3).  On-study visits may be completed within 	 5 days.  All PROs must 
be completed before any other study procedures for each visit.  The investigational 
product is to be administered following the completion of all other study-required 
procedures for that visit, inclusive of the long-term treatment period assessments. 
8.1.4 
Safety Follow-up Period 
A single safety follow-up visit may be required at 
per the Schedule of 
Activities (Table 1-4).  Refer to Section 4.1.3. 
CCI

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8.2 
General Assessments  
8.2.1 
Informed Consent 
All subjects or their legally authorized representative must sign and personally date the 
IRB/IEC and Amgen approved informed consent before any study-specific procedures 
are performed. 
8.2.2 
Demographics 
Demographic data collection including sex, age, race, and ethnicity will be collected in 
order to study their possible association with subject safety and treatment effectiveness.  
Additionally, the correlation between specific demographic data and PK, PD, and 
biomarkers may be explored. 
8.2.3 
Medical History 
The Investigator or designee will collect a relevant medical, psychiatric, and surgical 
history prior to enrollment or as necessary to describe chronic or co-morbid conditions 
through the start of the adverse event reporting period.  Medical history will include 
information on the subject's concurrent medical conditions.  Record all findings on the 
medical history CRF.  In addition to the medical history above, UC history must date 
back to the original diagnosis.  Normal stool frequency data will also be collected.  The 
current toxicity grade will be collected for each condition that has not resolved. 
8.2.4 
Physical Examination  
Physical examination will be performed as per standard of care.  Physical examination 
findings should be recorded on the appropriate CRF (eg, medical history, event). 
8.2.5 
Physical Measurements 
Height in centimeters and weight in kilograms should be measured without shoes. 
8.2.6 
Substance Abuse History  
Obtain a history of prior and/or concurrent use of alcohol and tobacco. 
Note:  subjects who are taking methotrexate must be advised to limit alcohol 
consumption to no more than 4 ounces per week. 
8.2.7 
Columbia Suicide Severity Rating Scale 
The baseline version of the C-SSRS will be administered at screening. 
The C-SSRS is a clinician rating of suicidal behavior and ideation.  The C-SSRS 
consists of a maximum of 20 items, which defines 5 subtypes of suicidal ideation and 
behavior in addition to self-injurious behavior with no suicidal intent.  The C-SSRS will be 
administered by the principal investigator or qualified designee.  Reports of suicidal 

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ideation with intent to act (severity of 4 or 5) and reports of actual, aborted, or interrupted 
suicide attempts or a behavior preparatory for making an attempt indicate subjects at 
high risk for suicide.  If such reports are identified at screening, it is an exclusion criterion 
and the subject is not eligible for the study. 
8.3 
Efficacy Assessments 
Specific efficacy assessments and time points are summarized in the Schedule of 
Activities (Table 1-1, Table 1-2, and Table 1-3). 
8.3.1 
Mayo Score (Total, Modified, and Partial) 
The total Mayo score is a composite index of 4 items (stool frequency, rectal bleeding, 
*3)48(45>+.3).3,8&3)5->8.(.&3H8,14'&1&88*882*39<.9-*&(-.9*2,7&)*)
semi-quantitatively on a score of 0 to 3 for a maximal total score of 12.  Scores range 
from 0 to 12 points.  The Mayo Daily Symptom Diary will be used to record stool 
frequency and rectal bleeding.  Refer to Appendix 10 for full definitions of Mayo 
subscores. 
#-*24).+.*)&>48(47*.89-*&>48(47*<.9-4:99-*5->8.(.&3H8,14'&1&88*882*39
subscore and ranges from 0 to 9 points.  The modified Mayo score will be used to 
assess primary and secondary efficacy endpoints.   
The partial Mayo score is the total Mayo score without the endoscopy subscore and 
ranges from 0 to 9 points. 
The rectal bleeding and stool frequency subscores will be derived from the last 3 days of 
data entered within the last 7 days prior to the visit, or within 7 days prior to initiation of 
bowel preparations for visits which include an endoscopy. 
Calculation of the modified Mayo score at screening to determine eligibility must use the 
stool frequency and rectal bleeding diary data from the most recent 3 days within the 7 
days prior to initiation of bowel preparations for the eligible screening endoscopy.  Bowel 
preparations should not be initiated if the combined sum of the rectal bleeding subscore 
&3)89441+7*6:*3(>8:'8(47*.8349B	!*+*794Appendix 10 for Mayo Scoring System 
for the Assessment of Ulcerative Colitis Activity. 
8.3.1.1 
Mayo Daily Symptom Diary 
Mayo daily symptom diaries will be provided to each subject to record stool frequency, 
and episodes of rectal bleeding.  Subjects will be instructed to complete the diary daily 
except upon commencing bowel preparation for endoscopy.  Recommence daily diary 
entries upon completion of the endoscopy. 

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8.3.1.2 
Endoscopy 
For the purposes of this study, a rectosigmoidoscopy or colonoscopy will be performed 
as part of the total and modified Mayo Score.  At the week 12 and 52/ET visits, a 
colonoscopy can be performed instead of rectosigmoidoscopy for clinically indicated 
reasons in the judgement of the investigator and after discussion with the Amgen 
physician as appropriate.  The procedure can be performed by the investigator or 
qualified designee using the institution's standard procedure and study manual.  The 
screening endoscopy must be performed approximately 14 days and no sooner than 
5 days (to enable results from the endoscopy central reader to be obtained and reviewed 
by the site) prior to the day 1 visit.  Subjects who do not have an up-to-date colorectal 
cancer surveillance colonoscopy in source document will have a colonoscopy instead of 
a rectosigmoidoscopy at screening per inclusion criteria 105. 
All rectosigmoidoscopies (or if applicable colonoscopy) will be read locally by the 
investigator (or designee).  In addition, video-recording of rectosigmoidoscopies (or if 
applicable colonoscopy) performed at screening, week 12, and at the week 52 visit, will 
be sent to a central reader for determination of the endoscopic component of the Mayo 
score.  Separate instructions on procedures and data collection for central reading of 
rectosigmoidoscopies will be provided to the site.  Central reading assessment at 
screening, week 12, and week 52 visit will be combined with the site assessment of 
(1.3.(&1.3).(*84+9-*&>48(47*89441+7*6:*3(>7*(9&1'1**).3,5->8.(.&3H8,14'&1
assessment) to compute the total or modified Mayo score (without the physician's global 
assessment) for that given visit. 
Rectosigmoidoscopies (or if applicable colonoscopies) performed at early termination 
will require central reading. 
For the purposes of treatment assignment into the long-term treatment period, clinical 
response will be assessed using the modified Mayo score and the endoscopic subscore 
assigned by the investigator (refer to Section 6.1.1.2). 
8.3.1.3 

	 
#-*5->8.(.&3H8,14'&1&88*882*39&(034<1*),*89-*
 other Mayo subscores, the 
5&9.*39H87*(&114+&')42.3&1).8(42+479&3),*3*7&18*38*4+<*11-being, and other 
observations, such as physical findings &3)9-*5&9.*39H85*7+472&3(*89&9:8 

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8.3.2 
Histopathology via Mucosal Biopsy 
Biopsy specimens for evaluation of the histologic endpoints will be obtained from the 
area of most severe inflammation in the colon.  Refer to the Laboratory Manual for 
further details on collection and processing of mucosal biopsies. 
The histopathologic images will be read centrally in a blinded manner by a qualified 
pathologist, and scoring will be performed by using the Geboes Score.  Refer to 
histopathology central reading charter for further details. 
The Geboes score is an instrument that is used to standardize histologic assessment in 
UC.  It comprises 7 categories (or grades), each of which describes a histologic feature.  
These categories are as follows:  grade 0, structural (architectural change); grade 1, 
chronic inflammatory infiltrate; grade 2A, lamina propria eosinophils; grade 2B, lamina 
propria neutrophils; grade 3, neutrophils in epithelium; grade 4, crypt destruction; and 
grade 5, erosion or ulceration.  Each grade includes subscores that indicate the degree 
of abnormality seen for that histologic feature, with subscores of 0 indicating normal 
appearance and higher subscores indicating increasingly abnormal appearance 
(Geboes et al, 2000). 
8.3.3 
Clinical Outcome Assessments 
Any PROs administered according to the Schedule of Activities must be completed 
before any other study procedures, including assessment of weight.  Patient reported 
outcomes (PROs) will be administered on an electronic device. 
8.3.3.1 
 
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8.3.3.1.1 
 
8.3.3.1.2 
 
8.3.3.1.3 
 
8.3.3.2 
Inflammatory Bowel Disease Questionnaire 
The Inflammatory Bowel Disease Questionnaire (IBDQ) is a disease specific PRO 
instrument that measures health-related quality of life in patients with IBD (Guyatt et al, 
1989).  The IBDQ has been designed to be self-administered and completed in 
15 minutes by respondents 
 18 years of age.  The IBDQ covers the following 
dimensions: bowel symptoms (10 items), systemic symptoms (5 items), emotional 
function (12 items) and social function (5 items).  Items are scored on a 7-point Likert 
scale, yielding a global score in the range 32 to 224 (with higher scores indicating better 
quality of life). 
8.3.3.3 
EQ-5D-5L 
The EuroQol-5-Dimension 5 levels (EQ-5D-5L) questionnaire is a 2-page, standardized 
instrument for use as a measure of health outcome developed by the EuroQol group 
CCI
CCI
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(Rabin and de Charro, 2001).  It is comprised of a 5-dimension health status measure 
and a visual analogue scale.  The 5-dimension health status measure evaluates: 
mobility, self-care, usual activities, pain/discomfort, and anxiety/depression based on a 
5-level scale: no problems, slight problems, moderate problems, severe problems, an 
extreme problem.  The visual analogue scale records the subject's self-rated health on a 
vertical, the visual analogue scale where the endpoints are labelled 'Best imaginable 
health state' and 'Worst imaginable health state'.  The EQ-5D-5L takes about 3 minutes 
to complete. 
8.3.3.4 
Patient Global Impression of Change 
 &9.*395*7(*.;*)(-&3,*8.3(*9-*89&794+97*&92*39<.11'*2*&8:7*):8.3,9-*G &9.*39
14'&1257*88.434+-&3,* H"5*(.+.(&11>9-* (&59:7*85&9.*395*7(*.;*)
change in their UC symptoms since the start of treatment.  In addition, it can be used as 
an anchor to estimate the minimally important difference as well as the small, medium, 
and large changes detected by other instruments. 
8.3.3.5 
Patient Global Impression of Severity 
Pat.*395*7(*.;*)).8*&8*8*;*7.9><.11'*&88*88*):8.3,9-*G &9.*3914'&1257*88.43
4+"*;*7.9> "H"5*(.+.(&11>9-* "(&59:7*85&9.*395*7(*.;*).257*88.434+
severity of their UC symptoms.  In addition, the PGIS can be used as an anchor in 
differentiating clinically distinct groups of subjects. 
8.4 
Safety Assessments 
Planned time points for all safety assessments are listed in the Schedule of Activities 
(Table 1-1, Table 1-2, Table 1-3, and Table 1-4). 
8.4.1 
Vital Signs 
The following measurements must be performed: systolic/diastolic blood pressure, heart 
rate, respiratory rate, and temperature.  Subject must be in a supine or seated position in 
a rested and calm state for at least 5 minutes before blood pressure assessments are 
conducted.  The position selected for a subject should be the same that is used 
throughout the study and documented on the vital signs eCRF.  The temperature 
location should be oral, tympanic, axilla, or forehead (with oral preferred).  Once a 
location for temperature assessment is selected for a subject, the location should be the 
same throughout the study and documented on the vital signs eCRF.  Record all 
measurements on the vital signs eCRF. 

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8.4.2 
Electrocardiograms (ECGs) 
Subject must be in supine position in a rested and calm state for at least 5 minutes 
before ECG assessment is conducted.  If the subject is unable to be in the supine 
position, the subject should be in most recumbent position as possible.  The ECG must 
include the following measurements: heart rate, QRS, QT, QTc, and PR intervals.  The 
investigator or designee will review all ECGs.  Once signed, the original ECG tracing will 
be retained with the subject's source documents.  At the request of the sponsor, a copy 
of the original ECG will be made available to Amgen. 
8.4.3 
Clinical Laboratory Assessments 
Refer to Section 11.2 for the list of clinical laboratory tests to be performed and to the 
Schedule of Activities (Table 1-1, Table 1-2, Table 1-3, and Table 1-4) for the timing and 
frequency. 
The investigator is responsible for reviewing laboratory test results and recording any 
clinically relevant changes occurring during the study in the Event eCRF.  The 
investigator must determine whether an abnormal value in an individual study subject 
7*57*8*398&(1.3.(&11>8.,3.+.(&39(-&3,*+7429-*8:'/*(9H8'&8*1.3*;&1:*83,*3*7&1
abnormal laboratory findings without clinical significance (based on the investigator's 
clinical judgment) are not to be recorded as adverse events.  However, laboratory value 
changes that require treatment or adjustment in current therapy are considered adverse 
events.  Where applicable, clinical sequelae (not the laboratory abnormality) are to be 
recorded as the adverse event. 
All protocol-required laboratory assessments, as defined in Section 11.2, must be 
conducted in accordance with the laboratory manual and the Schedule of Activities. 
Fecal calprotectin, fecal lactoferrin, high sensitivity C-reactive protein (hsCRP), central 
histology reads, antibody, PK, and lymphocyte subsets that are collected after 
randomization and could unblind the study will not be reported to investigative sites or 
other blinded personnel until the study has been unblinded. 
8.4.3.1 
Tuberculosis Testing 
All subjects must receive either a PPD, QuantiFERON-TB, or T-Spot test at screening.  
A chest X-ray will be performed for subjects with a positive tuberculosis test (ie, positive 
PPD or positive or indeterminate QuantiFERON-TB or T-spot test). 

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8.4.3.1.1 
Purified Protein Derivative 
The PPD test must be read by a trained health care professional 48 to 72 hours after the 
test is placed.  The PPD reader must be identified on the delegation of authority for this 
responsibility.  Purified protein derivative (PPD) test kits will not be provided by the 
sponsor and must be procured locally. 
8.4.3.1.2 
QuantiFERON-TB or T-Spot Testing 
If a QuantiFERON-TB test is performed for eligibility, the test will be performed either 
locally with test kits procured locally or centrally with the test kits provided.  If a T-Spot 
test is performed for eligibility, the test will be performed locally with the test kits 
procured locally. 
8.4.3.2 
HIV Antibodies, Hepatitis B, and Hepatitis C Testing 
HBsAb, HBsAg, HBcAb, HCAb, and HIV antibodies (where permitted by local 
regulations) will be assessed at screening.  If the results show a negative HBsAg and 
positive HBcAb and/or HBsAb, quantification of serum hepatitis B virus DNA by PCR is 
necessary.  Similarly, if the results show a positive HCAb, a quantification of serum 
hepatitis C virus RNA by PCR is necessary.  The above-mentioned PCR test results 
must be negative at screening for the subject to be eligible for this study.  Subjects 
positive for HBcAb and/or HBsAb without history of prior vaccination and without 
detectable serum Hepatitis B viral DNA by PCR are allowed to enroll, provided the 
subject undergoes monitoring of serum Hepatitis B viral DNA by PCR at every 2 months 
during the treatment period and up to 6 weeks after the end of treatment for the study.  
Subjects with a history of hepatitis B vaccination without history of hepatitis B infection 
(ie, positive HBsAb, negative HBsAg, and negative HBcAb) are allowed to enroll. 
8.4.3.3 
Fecal Calprotectin, Fecal Lactoferrin, C Difficile Toxin and Enteric 
Pathogen Testing 
Whole stool specimens will be collected within the 3 days prior to or during the study visit 
for quantitative determination of fecal calprotectin and fecal lactoferrin levels.  Stool 
samples must be collected prior to preparation of bowel for endoscopies.  Stool samples 
will be delivered to the sites by the subjects, and subsequently processed and shipped 
to the central laboratory for testing.  Detailed sample collection instructions for the 
subjects, and sample processing and shipping instructions for the sites, will be provided 
in the central laboratory manual.  Fecal calprotectin or lactoferrin information that would 
potentially unblind the study will not be reported to investigative sites or blinded 
personnel until the study has been unblinded. 

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Stool specimens will be tested at screening for C difficile toxin and other enteric 
pathogens including ova, parasites, Campylobacter, salmonella, shigella, E. Coli 
0157:H7, and Yersinia enterocolitica as specified in the laboratory manual. 
Stool sample must be collected and results available before the day 1 visit. 
8.4.4 
Adverse Events and Serious Adverse Events  
The method of recording, evaluating, and assessing causality of adverse events and 
serious adverse events and the procedures for completing and transmitting serious 
adverse event reports are provided in Section 11.4. 
8.4.4.1 
Time Period and Frequency for Collecting and Reporting Safety 
Event Information 
8.4.4.1.1 
Adverse Events 
The adverse event grading scale to be used for this study will be the Common 
Terminology Criteria for Adverse Events (CTCAE) and is described in Section 11.4. 
The investigator is responsible for ensuring that all adverse events observed by the 
investigator or reported by the subject that occur after first dose of investigational 
product through the end of study are reported using the Events eCRF. 
8.4.4.1.2 
Serious Adverse Events 
The investigator is responsible for ensuring that all serious adverse events observed by 
the investigator or reported by the subject that occur after signing of the informed 
consent through the end of study are reported using the Events eCRF. 
All serious adverse events will be collected, recorded and reported to the sponsor or 
designee .22*).&9*1>&3)341&9*79-&3	-4:784+9-*.3;*89.,&947H8&<&7*3*884+9-*
event, as indicated in Section 11.4.  The investigator will submit any updated serious 
adverse event data to the sponsor immediately and no later than 24 hours of it being 
available. 
Since the criteria in the CTCAE grading scale differs from the regulatory criteria for 
serious adverse events, if adverse events correspond to grade 4 CTCAE toxicity grading 
scale criteria (eg, laboratory abnormality reported as grade 4 without manifestation of life 
9-7*&9*3.3,89&9:8.9<.11'*1*+9949-*.3;*89.,&947H8/:),2*3994&1847*54799-*8*
abnormalities as serious adverse events.  For any adverse event that applies to this 
8.9:&9.43(4257*-*38.;*)4(:2*39&9.434+9-**;*39H88*;*7.9>2:89'*7*(47)*).39-*
subject medical records. 

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8.4.4.1.3 
Serious Adverse Events After the Protocol Required Reporting 
Period 
There is no requirement to actively monitor study subjects after the study has ended with 
regards to study subjects treated by the investigator.  However, if the investigator 
becomes aware of serious adverse events suspected to be related to investigational 
product these serious adverse events will be reported to Amgen immediately and no 
1&9*79-&3	-4:78+4114<.3,9-*.3;*89.,&947H8&<&7*3*884+9-**;*398 
Serious adverse events reported after the end of the study will be captured within the 
safety database as clinical trial cases and handled accordingly based on relationship to 
investigational product. 
If further safety related data is needed to fulfill any regulatory reporting requirements for 
a reportable event, then additional information may need to be collected from the 
8:'/*(9H87*(47)8&+9*79-*8:'/*(9*3)89-*89:)> 
8.4.4.2 
Method of Detecting Adverse Events and Serious Adverse Events 
Care will be taken not to introduce bias when detecting adverse events and/or serious 
adverse events.  Open-ended and non-leading verbal questioning of the subject is the 
preferred method to inquire about adverse event occurrence. 
8.4.4.3 
Follow-up of Adverse Events and Serious Adverse Events 
After the initial adverse event/serious adverse event report, the investigator is required to 
proactively follow each subject at subsequent visits/contacts.  All adverse events and 
serious adverse events will be followed until resolution, stabilization, until the event is 
otherwise explained, or the subject is lost to follow-up (as defined in Section 7.3).  
Further information on follow-up procedures is given in Section 11.4. 
All new information for previously reported serious adverse events must be sent to 
Amgen immediately and no later than 24 hours following awareness of the new 
information.  If specifically requested, the investigator may need to provide additional 
follow-up information, such as discharge summaries, medical records, or extracts from 
the medical records.  Information provided about the serious adverse event must be 
consistent with that recorded on the Events eCRF. 
8.4.4.4 
Regulatory Reporting Requirements for Safety Information 
If subject is permanently withdrawn from investigational product(s), and/or non-
investigational product(s)/auxiliary medicinal product(s) because of a serious adverse 
event, this information must be submitted to Amgen. 

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Prompt notification by the investigator to the sponsor of serious adverse events is 
essential so that legal obligations and ethical responsibilities towards the safety of 
subjects and the safety of a study treatment 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 treatment under clinical 
investigation.  The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IRBs/IECs, and investigators. 
Individual safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
An investigator who receives an individual safety report describing a serious adverse 
event or other specific safety information (eg, summary or listing of serious adverse 
*;*398+7429-*8543847<.11+.1*.9&143,<.9-9-*3;*89.,&947H874(-:7*&3)<ill notify 
the IRB/IEC, if appropriate according to local requirements. 
For studies in which the treatment assignment is blinded, to comply with worldwide 
reporting regulations for serious adverse events, the treatment assignment of subjects 
who develop serious, unexpected, and related adverse events may be unblinded by 
Amgen before submission to regulatory authorities.  Aggregate analyses may also be 
unblinded by the Safety Assessment Team, as appropriate.  Investigators will receive 
notification of related serious adverse events reports sent to regulatory authorities in 
accordance with local requirements. 
Amgen will prepare a single Development Safety Update Report (DSUR) (also referred 
to as Annual Safety Report [ASR] in the European Union) for the Amgen Investigational 
Product.  In order to ensure that consolidated safety information for the trial is provided, 
this single DSUR will also include appropriate information on any other investigational 
products used in the clinical trial, if applicable. 
8.4.4.5 
Safety Monitoring Plan 
":'/*(98&+*9><.11'*74:9.3*1>243.947*)&8)*+.3*).32,*3H88&+*9>8:7;*.11&3(*&3)
signal management processes. 
8.4.4.6 
Pregnancy and Lactation 
Details of all pregnancies and/or lactation in female subjects and female partners of 
male subjects will be collected after the start of study treatment and through 6 weeks 
after the last dose of investigational product. 

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If a pregnancy is reported, the investigator is to inform Amgen immediately and no later 
than 24 hours of learning of the pregnancy and/or lactation and is to follow the 
procedures outlined in Section 11.5.  Amgen Global Patient Safety will follow-up with the 
investigator regarding additional information that may be requested. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, and ectopic pregnancy) are considered serious adverse events. 
Further details regarding pregnancy and lactation are provided in Section 11.5. 
Pregnancy Testing 
A highly sensitivity (urine or serum) pregnancy test should be completed at screening 
and within 7 days of initiation of investigational product for females of childbearing 
potential. 
Note:  Females who have undergone a bilateral tubal ligation/occlusion should have 
pregnancy testing per protocol requirements.  If a female subject, or the partner of a 
male subject, becomes pregnant it must be reported on the Pregnancy Notification 
Form, see 
.  Refer to Section 11.5 for contraceptive requirements. 
Additional pregnancy testing using a high sensitivity urine pregnancy test should be 
performed at every 4 week intervals during treatment with investigational product and at 
the follow-up safety assessment and recorded on the eCRF. 
Additional on-97*&92*3957*,3&3(>9*89.3,2&>'*5*7+472*)&99-*.3;*89.,&947H8
discretion or as required per local laws and regulations. 
8.5 
Pharmacokinetic Assessments 
All subjects randomized to efavaleukin alfa will have PK samples assessed. 
Blood samples will be collected for measurement of serum concentrations of efavaleukin 
alfa as specified in the Schedule of Activities (Table 1-1 and Table 1-2). 
Instructions for the collection and handling of biological samples will be provided by the 
sponsor.  The actual date and time (24-hour clock time) of each sample will be recorded. 
Drug concentration information that would potentially unblind the study will not be 
reported to investigative sites or blinded personnel until the study has been unblinded. 
8.6 
Pharmacogenetic Assessments (Optional Consent) 
If the subject consents to the optional pharmacogenetic portion of this study, DNA 
analyses may be performed.  These optional pharmacogenetic analyses focus on 
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inherited genetic variations to evaluate their possible correlation to the disease and/or 
responsiveness to the therapies used in this study.  The goals of the optional studies 
include the use of genetic markers to help in the investigation of inflammatory conditions 
and/or to identify subjects who may have positive or negative response to efavaleukin 
alfa.  Additional samples are not collected for this part of the study.  For subjects who 
consent to this/these analysis/analyses, DNA may be extracted. 
The final disposition of samples will be described in Section 11.6. 
8.7 
Antibody Testing Procedures 
Blood sample(s) for antibody testing are to be collected according to the time points 
specified in the Schedule of Activities (Table 1-1, Table 1-2, Table 1-3, and Table 1-4) 
for the measurement of anti-efavaleukin alfa antibodies.  Samples testing positive for 
binding antibodies will also be tested for neutralizing antibodies and may be further 
characterized.  Additional blood samples may be obtained to rule out anti-efavaleukin 
alfa antibodies during the study. 
Subjects who test positive for anti-efavaleukin alfa antibodies that cross-react with and 
neutralize native human IL-2 at the final scheduled study visit will be asked to return for 
additional follow up testing.  This testing is to occur approximately every 3 months 
starting from the final scheduled antibody point and continue until: (1) IL-2 neutralizing 
antibodies are no longer detectable; or (2) the subject has been followed for a period of 
at least 1 year (	 4 weeks) post administration of efavaleukin alfa.  All follow-up results, 
both positive and negative will be communicated to the sites.  This notification is 
independent of and may be in advance of the time point when the entire study is 
unblinded.  Notification of a requirement for antibody follow-up testing is not unblinding 
since both placebo and dosed subjects will be monitored for antibodies using the same 
testing scheme, and binding and neutralizing antibodies to IL-2 are known to exist in 
healthy subjects and subjects with autoimmune disease (Shao and Gao, 2019; Perol et 
al, 2016; Watanabe et al, 2007; Balsari and Caruso, 1997). 
More frequent testing or testing for a longer period of time may be requested in the event 
of safety-related concerns. 
Refer to the laboratory manual for detailed collection and handling instructions. 

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8.8 
Biomarkers  
Biomarkers are objectively measured and evaluated indicators of normal biologic 
processes, pathogenic processes, or pharmacologic responses to a therapeutic 
intervention. 
8.8.1 
Pharmacodynamic Assessments 
Samples will be collected to understand the mechanism of action and biological effects 
of administration of efavaleukin alfa. 
Lymphocytes subsets:  Blood samples will be collected for all subjects at the time points 
indicated in the Schedule of Activities (Table 1-1, Table 1-2, and Table 1-3).  These 
samples will be used to evaluate the fold changes from baseline of Treg, CD4 Tcon, 
CD8 T cells, and NK absolute cell counts (cells/L) after efavaleukin alfa 
administration. 
Pharmacodynamic information that would potentially unblind the study will not be 
reported to the investigative sites or blinded personnel until the study has been 
unblinded. 
8.8.2 
Biomarker Development 
Samples will also be collected to develop or address biomarker hypotheses related to 
efavaleukin alfa activity, eg, to evaluate potential biomarkers that may correlate with 
treatment response. 
Blood and mucosal biopsy samples will be collected for biomarker development at the 
time points specified in the Schedule of Activities (Table 1-1, Table 1-2, and Table 1-3).   
Biomarker mucosal biopsy:  Biopsy for biomarker development will be performed at the 
time points indicated in the Schedule of Activities (Table 1-1, Table 1-2, and Table 1-3).  
Biopsy specimens for biomarker development will be obtained at the same time as the 
mucosal biopsy for histologic assessment.  Refer to Section 11.6 for more information. 
8.8.3 
Biomarker Future Research 
Future research can be useful in developing markers to identify disease subtypes, guide 
therapy, and/or predict disease severity.   
If consent is provided by subjects, any remaining samples collected at the time points 
specified in the Schedule of Activities, including samples collected for biomarker 
assessments may be used for future research as described in Appendix 6 
(Section 11.6).  No additional samples will be collected for future research. 

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Amgen or another third-party manufacturer may attempt to develop test(s) designed to 
identify subjects most likely to respond positively or negatively to efavaleukin alfa to 
investigate and further understand the inflammatory conditions. 
8.9 
Medical Resource Utilization and Health Economics 
Medical resource utilization and health economics data, associated with medical 
encounters, will be collected in the eCRF by the investigator and study-site personnel for 
all subjects throughout the study.  Protocol-mandated procedures, tests, and encounters 
are excluded. 
The data collected may be used to conduct exploratory economic analyses and will 
include: 
 
Number and duration of UC-related medical care encounters, including surgeries 
(eg, colectomy), and other selected procedures (inpatient and outpatient) 
 
Duration of UC-related hospitalization (total days or length of stay) 
9. 
Statistical Considerations 
9.1 
Statistical Hypotheses 
The primary hypothesis is that at least 1 efavaleukin alfa dose will have greater efficacy 
compared to placebo as measured by clinical remission rate at week 12 in subjects with 
moderately to severely active UC. 
9.2 
Sample Size Determination 
The planned sample size of 240 subjects provides approximately
 
 
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9.3 
Populations for Analysis 
 
Population 
Description 
Full Analysis Set 
All subjects randomized, analyzed by planned treatment 
group 
Safety Analysis Set 
All subjects randomized and received at least 1 dose of 
investigational product, analyzed by actual treatment group 
 
9.3.1 
Covariates 
The impact of baseline covariates on the treatment effect may be explored and adjusted 
in the model for the primary and secondary endpoints as deemed necessary. 
The baseline covariates include, but are not limited to the following: 
 
Stratification factors 
- 
Prior experience with at least 1 biologic or targeted small molecule: (yes, no) 
- 
Corticosteroid use at randomization: (yes, no) 
 
Age (>*&78B>*&78 
 
Sex (female, male) 
 
Race (white, non-white) 
 
Geographic region (Eastern Europe, Asia Pacific, Rest of World) 
 
Mayo score at baseline 
 
Disease localization (proctosigmoiditis, left-sided colitis, extensive colitis, pancolitis) 
 
Duration of UC (years from date of diagnosis to first dose date) 
Stratification factors will be included as covariates in the model.  If included as 
covariates in the model for treatment comparisons, the IRT value will be used to be 
consistent with the randomization scheme. 
9.3.2 
Subgroups 
In addition to stratification factors, some covariates, not limited to those mentioned in 
Section 9.3.1, may be used for further exploration in subgroups. 
9.4 
Statistical Analyses 
The statistical analysis plan will be developed and finalized before database lock.  Below 
is a summary of the timing and methods for the planned statistical analyses. 

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9.4.1 
Planned Analyses 
9.4.1.1 
Interim Analysis and Early Stopping Guidelines 
Interim analyses will be conducted to assess for futility.  Interim analyses will be 
conducted by an external Independent Biostatistics Group and results evaluated by an 
independent DMC (Section 11.3).  In the case where prespecified decision rules are met 
at a planned interim analysis, Amgen may review the unblinded results to endorse a final 
decision.  Details will be described in a Data Access Plan. 
Data from the interim analyses may also be analyzed to support dose selection or other 
activities related to further development, prior to the primary analysis.  The interim data 
will be analyzed by an internal Amgen team, separate from the study team.  Measures 
will be taken and documented to ensure these individuals who access restricted data for 
this purpose are separate from the study team. 
Data will be subject to ongoing checks for integrity, completeness and accuracy in 
accordance with the Data Management Plan with the expectation that outstanding data 
issues are resolved ahead of each interim analysis to the extent possible.   
In addition to the planned interim analyses, the DMC will regularly review the 
accumulating safety data to ensure the continuing safety of study subjects.  The first 
2 DMC meetings will occur after the first 20 subjects randomized have had the 
opportunity to complete the 
 and week 12 visits.  Thereafter the DMC will plan to 
meet approximately every 3 months until Amgen is unblinded at the primary analysis.  
After Amgen is unblinded, the DMC will plan to meet every 6 months.  Ad hoc meetings 
can be scheduled as needed.  The DMC will also review all available safety and efficacy 
data for interim analyses.  Additional details will be described in the DMC charter. 
9.4.1.2 
Primary Analysis 
The primary analysis will occur after all subjects have completed the week 12 visit or 
have early terminated.  The primary objective of the primary analysis is to evaluate the 
effect of efavaleukin alfa on induction of clinical remission.  All secondary objectives will 
also be evaluated at the time of the primary analysis. 
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Data will be subject to ongoing checks for integrity, completeness and accuracy in 
accordance with the Data Management Plan with the expectation that outstanding data 
issues are resolved ahead of the lock to the extent possible.  The data supporting the 
primary analysis will be locked to prevent further changes. 
9.4.1.3 
Final Analysis 
Final analysis activities will commence upon achieving the end of study as described in 
Section 4.4.  The final analysis will include analysis of efficacy and safety data collected 
during the exploratory long-term treatment period. 
Data will be subject to ongoing checks for integrity, completeness and accuracy in 
accordance with the Data Management Plan with the expectation that all outstanding 
data issues are resolved ahead of the final lock. 
9.4.2 
Methods of Analyses 
9.4.2.1 
General Considerations 
All categorical variables will be summarized using the number and percent of subjects 
falling into each category and all continuous variables will be summarized using mean, 
standard error or standard deviation, median, minimum, maximum, and number of 
subjects with observations. 
Unless specified otherwise, efficacy analyses will be summarized by randomized 
treatment group; and safety analyses will be summarized by actual treatment received. 
Nominal p-values will be reported for the primary and secondary efficacy endpoints, with 
no adjustment for multiplicity. 
9.4.2.2 
Efficacy Analyses 
 
Endpoint/ 
Estimand 
Statistical Analysis Methods 
Primary 
Logistic regression will be performed to test the difference in clinical 
remission rates between each efavaleukin alfa dose and placebo 
(Ge et al, 2011).  The stratification factors as captured in IRT will be 
included as covariates.  The estimate of the risk difference between 
each efavaleukin alfa dose and placebo, the corresponding 2-sided 
95 Wald confidence interval, and the p-value obtained from the 
logistic regression model will be provided.  Missing primary endpoint 
data will be imputed using nonresponder imputation. 
Secondary 
Clinical response, endoscopic remission, and combined endoscopic 
and histologic remission will be analyzed using the same methods as 
the primary estimand. 
Change from baseline in histologic score at week 12 will be analyzed 

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using an ANCOVA model with the stratification factors as capture in 
IRT as covariates. 
Exploratory 
Will be described in the statistical analysis plan finalized before 
database lock 
 
9.4.2.3 
Safety Analyses 
 
Endpoint 
Statistical Analysis Methods 
Secondary 
All safety analyses will be performed using the Safety Analysis Set 
'&8*)438:'/*(9H8actual treatment received.  Safety analysis will 
include analyses of adverse events, clinical laboratory tests, vital 
signs. 
 
9.4.2.3.1 
Adverse Events 
Subject incidence of all treatment-emergent adverse events will be tabulated by system 
organ class and preferred term.  Tables of fatal adverse events, serious adverse events, 
adverse events leading to discontinuation from investigational product or other 
protocol-required therapies, and significant treatment emergent adverse events will also 
be provided. 
9.4.2.3.2 
Laboratory Test Results 
The analyses of safety laboratory endpoints will include summary statistics over time by 
each treatment group.  Shifts in grades of safety laboratory values between baseline to 
the worst on-study value will be presented. 
9.4.2.3.3 
Vital Signs 
The analyses of vital signs will include summary statistics over time by treatment group. 
9.4.2.3.4 
Physical Measurements 
The analyses of physical measurements will include summary statistics over time by 
each treatment group. 
9.4.2.3.5 
Electrocardiogram 
The ECG measurements from this clinical study were performed as per standard of care 
for routine safety monitoring, rather than for purposes of assessment of potential QTc 
effect.  Since these evaluations may not necessarily be performed under the rigorous 
conditions expected to lead to meaningful evaluation of QTc data; summaries and 
statistical analyses of ECG measurements are not planned, and these data would not be 
expected to be useful for meta-analysis with data from other trials. 

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9.4.2.3.6 
Antibody Formation 
The incidence and percentage of subjects who develop anti-efavaleukin alfa antibodies 
and antibodies to IL-2 (binding and if positive, neutralizing) at any time will be tabulated 
by actual treatment received. 
9.4.2.3.7 
Exposure to Investigational Product 
Summary statistics will be provided for the total number of doses administered of 
investigational product exposure by treatment. 
9.4.2.3.8 
Exposure to Concomitant Medication 
Number and proportion of subjects receiving therapies of interest will be summarized by 
preferred term for each treatment group as coded by the World Health Organization 
Drug dictionary. 

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10. 
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Intern Med.  2014;160(10):704-711. 
+&;&1*:0.3&1+&3;*89.,&947H874(-:7*#-4:8&3)&082,*33( 
Feagan BG, Rutgeers P, Sands BE.  Vedolizumab as induction and maintenance 
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Ford AC, Bernstein CN, Khan KJ, et al.  Glucocorticosteroid therapy in inflammatory 
bowel disease:  systematic review and meta-analysis.  Am J Gastroenterol.  
2011;106(4):590-599. 
Fumery M, Singh S, Dulai PS, et al.  Natural history of adult ulcerative colitis in 
population-based cohorts: A systematic review.  Clin Gastroenterol Hepatol. 
2018;16:343C56.e3. 
Ge M, Durham LK, Meyer RD, Xie W, Thomas N.  Covariate-adjusted difference in 
proportions from clinical trials using logistic regression and weighted risk differences.  
Drug Inf J.  2011;45:481-493. 
Geboes K, Riddell R, Öst A, Jensfelt B, Persson, T, Löfberg R. A reproducible grading 
scale for histological assessment of inflammation in ulcerative colitis.  Gut. 
2000;47 :404-409. 
Guyatt G, Mitchell A, Irvine EJ, et al.  A new measure of health status for clinical trials in 
inflammatory bowel disease.  Gastroenterology.  1989 ;96(3) :804-810. 
Humrich J, von Spee-Mayer C, Siegert E, et al.  Rapid induction of clinical remission by  
low-dose interleukin-2 in a patient with refractory SLE.  Ann Rheum Dis.  2015;74: 
791-792. 
Kelsen J, Baldassano RN.  Inflammatory Bowel Disease:  The Difference Between 
Children and Adults.  Inflamm Bowel Dis.  2008;14(S2):S9-S11. 
Koreth J, Matsuoka K, Kim HT, et al.  Interleukin-2 and regulatory T cells in 
graft-versus-host-disease.  N Engl J Med.  2011;365(22):2055-2066. 

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Koreth J, Kim H, Jones K, et al.  Efficacy, durability, and response predictors of low-dose 
interleukin-2 therapy for chronic graft vs. host disease.  Blood.  2016.  
DOI:10.1182/blood-2016-02-702852. 
Malek TR, Castro I.  Interlekin-2 Receptor Signaling:  At the Interface between Tolerance 
and Immunity.  Immunity.  2010;33(2):153-165. 
Matsuoka KI, Koreth J, Kim HT, et al.  Low-dose interleukin-2 therapy restores 
regulatory T cell homeostasis in patients with chronic graft-versus-host disease.  Sci 
Transl.  2013;5(179):179ra43. 
Mosli MH, MacDonald JK, Bickston SJ, et al.  Vedolizumab for induction and 
maintenance of remission in ulcerative colitis:  a Cochrane systematic review and 
meta-analysis.  Inflamm Bowel Dis.  2015;21(5):1151-1159. 
Perol L, Lindner JM, Caudana P, et al. Loss of immune tolerance to IL-2 in type 1 
diabetes.  Nat. Commun. 2016; 7: 13027. 
Rabin R., de Charro, F. EQ-5D : a measure of health status from the EuroQoL Group.  
Ann Med.  2001;5 :337-343. 
Roda G, Narula N, Pinotti R, et al.  Systematic review with meta-analysis: Proximal 
disease extension in limited ulcerative colitis.  Aliment Pharmacol Ther.  2017;45:1481C
92. 
Rosenzwajg M, Lorenzon R, Cacoub P, et al.  Immunological and clinical effects of 
low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial.  
Ann Rheum Dis.  2019;78:209-217. 
Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD.  ACG Clinical 
Guideline:  Ulcerative Colitis in Adults.  Am J Gastroenterol.  2019;114(3):384-413. 
Saadoun D, Rosenzwajg M, Joly F, et al.  Regulatory T cell responses to low-dose 
interleukin-2 in HCV-induced vasculitis.  N Engl J Med.  2011;365;2067-2077. 
Sandborn WJ, Su C, Sands BE, et al.  Tofacitinib as Induction and Maintenance Therapy 
for Ulcerative Colitis.  N Engl J Med.  2017;376(18):1723-1736. 
"&3)'473%H&*38!%41+*9&1?&3.24)&83):(9.43#-*7&5>.3
Moderate-to-Severe Ulcerative Colitis:  Results from the Phase 3, Randomized, 
Double-blind, Placebo-controlled True North Study.  UEG 2020 Virtual Conference; 
11-13 October 2020.  Abstract LB02. 
Sands BE, Sandborn WJ, Panaccione R, et al.  Ustekinumab as Induction and 
Maintenance Therapy for Ulcerative Colitis.  N Engl J Med.  2019;381(13):1201-1214. 
Scherl EJ, Pruitt R, et al. Safety and efficacy of a new 3.3 g b.i.d.  tablet formulation in 
patients with mild-to-moderately-active ulcerative colitis: a multicenter, randomized, 
double-blind, placebo-controlled study. Am J Gastroenterol. 2009:104:1452-1459. 
Schroeder KW, Tremaine WJ, et al. Coated 5-aminosalicylic acid therapy for mildly to 
moderately active ulcerative colitis. A randomized study.  N Engl J Med. 
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regulating the immune balance of T cells.  Scand J Immunol. 2019;90(6):e12822. 
Stidham RW, Lee TCH, Higgins PDR, et al.  Systematic review with network 
meta-analysis:  the efficacy of anti-tumour necrosis factor-alpha agents for the treatment 
of ulcerative colitis.  Aliment Pharmacol Ther.  2014;39(7):660-671. 

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Tripathi K, Feuerstein JD.  New developments in ulcerative colitis:  latest evidence on 
management, treatment, and maintenance.  Drugs Context.  2019;8:212572. 
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2017;389:1756-1770. 
Wang Y, Parker CE, Bhanji T, Feagan BG, MacDonald JK.  Oral 5-aminosalicyclic acid 
for induction of remission in ulcerative colitis.  Cochrane Database Syst Rev.  
2016;4:CD000543.  DOI:10.1002/14651858.CD000543.pub4. 
Watanabe M, Uchida K, Nakagaki K, et al.  Anti-cytokine autoantibodies are ubiquitous 
in healthy individuals.  FEBS Letters. 2007; 581: 2017-2021.  
Yarur AJ, Rubin DT.  Therapeutic Drug Monitoring of Anti-tumor Necrosis Factor Agents 
in Patients with Inflammatory Bowel Diseases.  Inflamm Bowel Dis.  
2015;21(7):1709-1718. 
 

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11. 
Appendices 
11.1 
Appendix 1.  List of Abbreviations 
 
Abbreviation 
Explanation 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
ASA 
aminosalicylates 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
CFR 
U.S. Code of Federal Regulations 
cGvHD 
chronic graft versus host disease 
Cmax 
maximum observed concentration 
COVID-19 
Corona virus-19 
CRF 
case report form 
CRO 
contract research organization 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CTCAE 
Common Terminology Criteria for Adverse Events 
DILI 
drug induced liver injury 
DMC 
data monitoring committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
ET 
early termination 
ePRO 
electronic patient reported outcome 
EQ-5D-5L 
EuroQol-5-Dimension 5 levels 
eSAE 
electronic serious adverse event 
FSH 
follicle stimulating hormone 
GCP 
Good Clinical Practice 
GvHD 
graft versus host disease 
HBcAb 
hepatitis B core antibody 
HBsAb 
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HCAb 
hepatitis C antibody 
HIV 
human immunodeficiency virus 
hsCRP 
high sensitivity C-reactive protein 
IBD 
inflammatory bowel disease 
IBDQ 
Inflammatory Bowel Disease Questionnaire 
IBG 
Independent Biostatistics Group 

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ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IL-2 
interleukin-2 
INR 
international normalized ratio 
IQR 
inter-quartile range 
IRB 
Institutional Review Board 
IRT 
interactive response technology 
IV 
Intravaneous(ly) 
JAK 
Janus kinase 
NCT 
National Clinical Trials 
NK 
natural killer 
PCR 
Polymerase chain reaction 
PD 
pharmacodynamic 
PGIC 
Patient Global Impression of Change 
PGIS 
Patient Global Impression of Severity 
PK 
pharmacokinetic 
Placebo nonresponder 
A subject randomized to placebo who has not achieved clinical 
response by week 12 
Placebo responder 
A subject randomized to placebo who achieves clinical response 
at week 12 
PPD 
purified protein derivative 
PRO 
patient reported outcome 
QTL 
quality tolerance limit 
RA 
rheumatoid arthritis 
SC 
subcutaneous(ly) 
SLE 
Systemic lupus erythematosus 
SUSAR 
suspected unexpected serious adverse reaction 
TB 
tuberculosis 
TBL 
total bilirubin 
TNF 
tumor necrosis factor 
Treg 
regulatory T cells 
UC 
ulcerative colitis 
ULN 
upper limit of normal 
CCI
CCI
CCI

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VAS 
visual analogue scale 
 

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11.2 
Appendix 2.  Clinical Laboratory Tests 
The tests detailed in Table 11-1 will be performed by the central laboratory unless 
indicated as local laboratory.  Additional analyte test results may be reported by the local 
or central laboratory, in accordance with standard laboratory procedures (eg, 
components of a hematology panel). 
Protocol-specific requirements for inclusion or exclusion of subjects are detailed in 
Sections 5.1 to 5.2 of the protocol. 
Additional tests may be performed at any time during the study as determined necessary 
by the investigator or required by local regulations. 

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Table 11-1.  Analyte Listing 
Central Laboratory: 
Chemistry 
Central Laboratory: 
Hematology 
Central Laboratory: 
Urinalysis 
Other Labs 
Sodium 
Potassium 
Chloride 
Bicarbonate  
Total protein 
Albumin 
Calcium 
Adjusted calcium 
Magnesium 
Phosphorus 
Glucose 
BUN or Urea 
Total bilirubin 
Direct bilirubin 
ALP 
LDH 
AST (SGOT) 
ALT (SGPT) 
GGT 
Creatinine 
hsCRPa 
CK 
RBC 
Hemoglobin 
Hematocrit 
MCV  
MCH 
MCHC 
RDW 
Reticulocytes 
Platelets 
WBC 
Differential 
@&3)889&'8 
@48.345-.18 
@&845-.18 
@>25-4(>9*8 
@434(>9*8 
@#49&13*:9745-.18 
@"*,2*39*)
neutrophils 
Protein/creatinine ratio 
Specific gravity 
pH 
Blood 
Protein  
Glucose 
Bilirubin 
WBC 
RBC 
Epithelial cells 
Bacteria 
Casts 
Crystals 
 
Central Laboratory:  
Serum pregnancy 
FSH 
Quantiferon-TB 
(may be performed 
locally) 
Hep B surface 
antigen 
Hep B surface 
antibody 
Hep B core antibody 
Hep C antibody 
Hep B viral DNA PCR 
Hep C viral RNA PCR 
HIV antibody 
Fecal calprotectina 
Fecal lactoferrina 
Stool C difficile toxin 
& enteric pathogens 
Histopathology 
mucosal biopsya 
Anti-drug antibodies 
PK samples 
Biomarker 
development sample 
Biomarker mucosal 
biopsy 
Lymphocyte subseta 
PGx samples 
 
Local Laboratory: 
Urine Pregnancy 
PPD or T-spot 
Central Laboratory: 
Coagulation 
PT/INR 
aPTT 
ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
BUN = blood urea nitrogen; CK = creatinine kinase; FSH = follicle stimulating hormone; GGT = gamma 
glutamyl transferase; Hep = hepatitis; HIV = human immunodeficiency virus; HLA = human leukocyte 
antigen; hsCRP = high sensitivity C-reactive protein; INR = international normalized ratio; LDH = lactate 
dehydrogenase; MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin 
concentration; MCV = mean corpuscular volume; PCR = polymerase chain reaction; PGx = 
pharmacogenetic; PPD = purified protein derivative; PT = prothrombin time; PTT = partial thromboplastin 
time;  RBC = red blood cell count; RDW = Red cell distribution width; SGOT = serum glutamic-oxaloacetic 
transaminase; SGPT - serum glutamic-pyruvic transaminase; WBC = white blood cell count 
a To be kept blinded after randomization and until the study is unblinded. 
Laboratory results that could unblind the study will not be reported to investigative sites 
or other blinded personnel until the study has been unblinded.  Refer to Section 8.4.3 for 
a list of assessments that could unblind the study. 

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If the subject is being followed for possible drug induced liver injury (DILI), the following 
analytes may be tested at the local laboratory depending on the clinical situation (see 
Section 11.7): 
Table 11-2.  DILI Potential Analyte Listing 
Chemistry 
Total bilirubin, direct bilirubin, ALP, LDH, AST (SGOT), ALT (SGPT), 
creatine kinase, ferritin, gamma-glutamyl transferase, haptoglobin 
Hematology 
Hemoglobin, Platelets, RBC Morphology, WBC Count, WBC Differential 
Coagulation 
PT, INR 
Immunology 
5 Prime Nucleotidase, Alpha-1 Antitrypsin, Antinuclear Antibodies, Anti-
Smooth Muscle Antibody, Anti-Soluble Liver Ag/Liver-Pancreas Ag, 
Cytomegalovirus IgG Antibody, Cytomegalovirus IgM Antibody, Endomysial 
IgA Antibody, Epstein-Barr Virus EDA IgG Antibody, Epstein-Barr Virus NA 
IgG Antibody, Epstein-Barr Virus VCA IgG Antibody, Epstein-Barr Virus 
VCA IgM Antibody, Hepatitis A Virus IgG Antibody, Hepatitis A Virus IgM 
Antibody, Hepatitis B Core Antibodies, Hepatitis B Core IgM Antibody, 
Hepatitis B Surface Antigen, Hepatitis B Virus DNA Genotyping, Hepatitis B 
Virus Surface Antibody, Hepatitis C Antibodies, Hepatitis C Virus RNA 
Genotyping, Hepatitis D Virus Antibody, Hepatitis E IgG Antibody, Hepatitis 
E IgM Antibody, Herpes Simplex Virus Type 1_2 IgG AB, Herpes Simplex 
Virus Type 1_2 IgM AB, Human Herpes Virus 6 DNA, Human Herpes Virus 
7 DNA, Human Herpes Virus 8 DNA, Immunoglobulin G, Liver Kidney AB 1,  
Parvovirus IgM/IgG Antibody, Serum Caeruloplasmin, Tissue 
Transglutaminase IgA Antibody, Toxoplasma IgM/IgG, Varicella Zoster 
Virus Antibody 
Toxicology 
Acetaminophen 
ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; Ig = 
immunoglobulin; INR = international normalized ratio; LDH = lactate dehydrogenase; PT = prothrombin time; 
PTT = partial thromboplastin time; RBC = red blood cell; SGOT = serum glutamic-oxaloacetic transaminase; 
SGPT - serum glutamic-pyruvic transaminase; WBC = white blood cell 
 

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11.3 
Appendix 3.  Study Governance Considerations 
Data Monitoring Committee(s) 
The Data Monitoring Committee (DMC) is an independent, multidisciplinary group 
consisting of clinicians and biostatisticians that collectively have experience in the 
management of subjects with inflammatory disease including moderately to severely 
active ulcerative colitis (UC) and, in the conduct, and monitoring of randomized studies.  
The DMC will include at least 2 clinicians and 1 biostatistician.  An Independent 
Biostatistics Group (IBG) will perform the interim analyses and provide the interim report 
to an independent DMC.  The first 2 DMC meetings will occur after the first 20 subjects 
randomized have had the opportunity to complete the 
 and week 12 visits.  
Thereafter the DMC will plan to meet approximately every 3 months until Amgen is 
unblinded at the primary analysis.  After Amgen is unblinded, the DMC will plan to meet 
every 6 months.  Ad hoc meetings can be scheduled as needed.  The DMC will also 
review all available safety and efficacy data for interim analyses (see Section 9.4.1.1 for 
time points#-*&3)<.11-&;*&((*88948:'/*(98H.3).;.):&197*&92*39
assignments.  To minimize the potential introduction of bias to the conduct of the study, 
members of the DMC and IBG will not have any direct contact with study site personnel 
or subjects.  The DMC will communicate major safety concerns and recommendations 
regarding study modification or termination based on the safety and efficacy parameters 
to Amgen in accordance with the DMC charter. 
Records of all meetings will be maintained by the DMC for the duration of the study.  
Records of all meetings will be transferred and stored in the trial master folder at the 
conclusion of the study.  Further details are provided in the DMC charter. 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with: 
 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences International Ethical Guidelines 
 
Applicable International Council for Harmonisation (ICH) Good Clinical Practice 
(GCP) Guidelines 
 
Applicable ICH laws and regulations 
#-*57494(4157494(41&2*3)2*398.3+472*)(438*39+4723;*89.,&947H874(-:7*&3)
other relevant documents (eg, subject recruitment advertisements) must be submitted to 
an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) by the 
investigator and reviewed and approved by the IRB/IEC.  A copy of the written approval 
CCI

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of the protocol and informed consent form must be received by Amgen before 
recruitment of subjects into the study and shipment of Amgen investigational product. 
Amgen may amend the protocol at any time.  The investigator must submit and, where 
necessary, obtain approval from the IRB/IEC for all protocol amendments and changes 
to the informed consent document that Amgen distributes to the sites.  The investigator 
must send a copy of the approval letter from the IRB/IEC and amended protocol 
3;*89.,&947H8".,3&9:7*5&,*942,*357.4794.251*2*39&9.434+9-*57494(41
amendment at their site. 
During the course of the study, if new information becomes available that alters the 
benefit-risk of the study or the study drug, Amgen will follow applicable regulations to 
notify investigators, the IRB/IEC, and regulatory authorities, as appropriate. 
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 
 
Obtaining annual IRB/IEC approval/renewal throughout the duration of the study.  
45.*84+9-*.3;*89.,&947H87*54798&3)9-* IRB/IEC continuance of approval must be 
sent to Amgen 
 
Notifying the IRB/IEC of serious adverse events occurring at the site, deviations from 
the protocol or other adverse event reports received from Amgen, in accordance with 
local procedures 
 
Overall conduct of the study at the site and adherence to requirements of Title 21 of 
the U.S. Code of Federal Regulations (CFR), ICH guidelines, the IRB/IEC, and all 
other applicable local regulations 
Recruitment Procedures 
Site staff will identify potential subjects from their existing patient population or may seek 
referral patients through existing professional networks or other community sources such 
as advocacy groups.  All patient facing materials must be reviewed/approved by the 
sponsor (Amgen Inc.) and the local IRB/IEC. 
Informed Consent Process 
An initial sample informed consent form is provided for the investigator to prepare the 
informed consent document to be used at his or her site.  Updates to the sample 
informed consent form are to be communicated formally in writing from the Amgen Trial 
Manager to the investigator.  The written informed consent form is to be prepared in the 
language(s) of the potential patient population. 

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The investigator or his/her delegated representative will explain to the subject, or their 
legally authorized representative, the aims, methods, anticipated benefits, and potential 
hazards of the study before any protocol-specific screening procedures or any 
investigational product(s) is/are administered, and answer all questions regarding the 
study.   
Subjects must be informed that their participation is voluntary.  Subjects or their legally 
authorized representative will then 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 requirements, where applicable, and the 
IRB/IEC or study site. 
The medical record must include a statement that written informed consent was obtained 
before the subject was enrolled in the study and the date the written consent was 
obtained.  The authorized person obtaining the informed consent must also sign the 
informed consent form. 
The investigator is also responsible for asking the subject if the subject has a primary 
care physician and if the subject agrees to have their primary care physician informed of 
9-*8:'/*(9H85&79.(.5&9.43.39-*(1.3.(&189:)>:31*88.9.8&14(&17*6:.7*2*39#-*
investigator shall then inform the primary care physician.  If the subject agrees to such 
349.+.(&9.439-*.3;*89.,&947.894.3+4729-*8:'/*(9H857.2&7>(&7*5->8.(.&34+9-*
8:'/*(9H85&79.(.5&9.43.39-*(1.3.(&189:)>+9-*8:'/*(9)4*8349-&;*&57.2&7>(&7*
physician and the investigator will be acting in that capacity, the investigator is to 
)4(:2*398:(-.39-*8:'/*(9H82*).(&17*(47) 
The acquisition of informed consent &3)9-*8:'/*(9H8&,7**2*39477*+:8&14+9-*.7
notification of the primary care physician .894'*)4(:2*39*).39-*8:'/*(9H82*).(&1
records, and the informed consent form is to be signed and personally dated by the 
subject or a legally authorized representative and by the person who conducted the 
informed consent discussion.  Subject withdrawal of consent or discontinuation from 
89:)>97*&92*39&3)47574(*):7*82:89&184'*)4(:2*39*).39-*8:'/*(9H82*).(&1
records; refer to Section 7. 
Subjects must be re-consented to the most current version of the informed consent 
form(s) during their participation in the study.  

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The original signed informed consent form is to be retained in accordance with 
institutional policy, and a copy of the informed consent form(s) must be provided to the 
8:'/*(9479-*8:'/*(9H81*,&11>&:9-47.?*)7*57*8*39&9.;* 
A subject who is rescreened is not required to sign another informed consent form if the 
rescreening occurs within 35 days from the previous informed consent form signature 
date. 
The informed consent form will contain a separate section that addresses the use of 
remaining mandatory samples for optional future research.  The investigator or 
authorized designee will explain to each subject the objectives of the future research.  
Subjects will be told that they are free to refuse to participate and may withdraw their 
specimens at any time and for any reason during the storage period.  A separate 
8.,3&9:7*<.11'*7*6:.7*)94)4(:2*39&8:'/*(9H8&,7**2*39 to allow any remaining 
specimens to be used for future research.  Subjects who decline to participate will not 
provide this separate signature. 
Data Protection/Subject Confidentiality 
#-*.3;*89.,&9472:89*38:7*9-&99-*8:'/*(9H8confidentiality is maintained for 
documents submitted to Amgen. 
The subject will be assigned a unique identifier by the sponsor.  Any subject records or 
datasets that are transferred to the sponsor will contain the identifier only; subject names 
or any information which would make the subject identifiable will not be transferred.  
On the Case Report Form (CRF) demographics page, in addition to the unique subject 
identification number, include the age at time of enrollment. 
For serious adverse events reported to Amgen, subjects are to be identified by their 
unique subject identification number, initials (for faxed reports, in accordance with local 
laws and regulations), and age (in accordance with local laws and regulations). 
Documents that are not submitted to Amgen (eg, signed informed consent forms) are to 
be kept in confidence by the investigator, except as described below. 
Subject data should be kept in a secure location.  Access to subject data will be limited 
to authorized individuals, as described below. 
In compliance with governmental regulations/ICH GCP Guidelines, it is required that the 
investigator and institution permit authorized representatives of the company, of the 
regulatory agency(s), and the IRB/IEC ).7*(9&((*88947*;.*<9-*8:'/*(9H847.ginal 

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medical records for verification of study-related procedures and data.  Direct access 
includes examining, analyzing, verifying, and reproducing any records and reports that 
are important to the evaluation of the study. 
The investigator is obligated to inform and obtain the consent of the subject to permit 
such individuals to have access to their study-related records, including personal 
information. 
Amgen complies with all relevant and applicable laws and regulations that protect 
personal information in order to ensure subject confidentiality and privacy.  Subjects are 
)*8.,3&9*)'>&:3.6:*8:'/*(9.)*39.+.(&9.433:2'*7.39-*"543847H88>89*28#-*
Sponsor uses access-controlled systems to house, review and analyze subject data.  
These systems are backed-up regularly to minimize the risk of loss of subject data; 
procedures are also defined for data recovery in the event of data loss.  The Sponsor 
has standard operating procedures in place that restrict access to subject data to those 
who require access to this data based on their role and have also completed the 
required training.  These procedures also outline the process for revoking access to 
such data when it is no longer needed.  In the event of a security breach, the Sponsor 
has procedures in place for notification of privacy incidents and to address these 
incidents, via its Business Conduct Hotline. 
Publication Policy 
To coordinate dissemination of data from this study, Amgen may facilitate the formation 
of a publication committee consisting of several investigators and appropriate Amgen 
staff, the governance and responsibilities of which are set forth in a Publication Charter.  
The committee is expected to solicit input and assistance from other investigators and to 
collaborate with authors and Amgen staff, as appropriate, as defined in the Publication 
Charter.  Membership on the committee (both for investigators and Amgen staff) does 
not guarantee authorship.  The criteria described below are to be met for every 
publication. 
Authorship of any publications resulting from this study will be determined on the basis 
of the Uniform Requirement for Manuscripts Submitted to Biomedical Journals 
International Committee of Medical Journal Editors Recommendations for the Conduct of 
Reporting, Editing, and Publications of Scholarly Work in Medical Journals, which states:  
Authorship credit is to be based on:  (1) substantial contributions to conception and 
design, acquisition of data, or analysis and interpretation of data; (2) drafting the article 
or revising it critically for important intellectual content; (3) final approval of the version to 

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be published; and (4) agreement to be accountable for all aspects of the work in 
ensuring that questions related to the accuracy or integrity of any part of the work are 
appropriately investigated and resolved.  Authors need to meet conditions 1, 2, 3, and 4. 
When a large, multicenter group has conducted the work, the group is to identify the 
individuals who accept direct responsibility for the manuscript.  These individuals must 
fully meet the criteria for authorship defined above.  Acquisition of funding, collection of 
data, or general supervision of the research group, alone, does not justify authorship.  All 
persons designated as authors must qualify for authorship, and all those who qualify are 
to be listed.   Each author must have participated sufficiently in the work to take public 
responsibility for appropriate portions of the content.  All publications (eg, manuscripts, 
abstracts, oral/slide presentations, book chapters) based on this study must be 
submitted to Amgen for review.  The Clinical Trial Agreement among the institution, 
.3;*89.,&947&3)2,*3<.11)*9&.19-*574(*):7*8+47&3)9.2.3,4+2,*3H87*;.*<4+
publications. 
Investigator Signatory Obligations 
Each clinical study report is to be signed by the investigator or, in the case of multicenter 
studies, the coordinating investigator. 
The coordinating investigator, identified by Amgen, will be any or all of the following: 
 
A recognized expert in the therapeutic area 
 
An Investigator who provided significant contributions to either the design or 
interpretation of the study 
 
An Investigator contributing a high number of eligible subjects 
Data Quality Assurance 
All subject data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data, centrally or 
adjudicated data).  The investigator is responsible for verifying that data entries are 
accurate and correct by physically or electronically signing the CRF. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
The sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 

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Clinical monitors will perform ongoing source data verification to confirm that data 
entered into the CRF by authorized site personnel are accurate, complete, and verifiable 
from source documents; that the safety and rights of subjects 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 per 
9-*8543847H8243.947.3,51&3 
The investigator agrees to cooperate with the clinical monitor to ensure that any 
problems detected in the course of these monitoring visits, including delays in 
completing CRFs, are resolved. 
The Amgen representative(s) and regulatory authority inspectors are responsible for 
contacting and visiting the investigator for the purpose of inspecting the facilities and, 
upon request, inspecting the various records of the clinical study (eg, CRFs and other 
pertinent data) provided that subject confidentiality is respected. 
3&((47)&3(*<.9- &3)9-*8543847H8&:).951&389-.889:)>2&>'*8*1*(9*)
for audit by r*57*8*39&9.;*8+7422,*3H814'&1!*8*&7(-&3)*;*1452*39
Compliance and Audit function (or designees).  Inspection of site facilities (eg, 
pharmacy, protocol-required therapy storage areas, laboratories) and review of 
study-related records will occur to evaluate the study conduct and compliance with the 
protocol, ICH GCP, and applicable regulatory requirements. 
Quality tolerance limit (QTL) parameters will be pre-defined in the QTL definitions table 
to identify possible systematic issues that can impact participant safety and/or reliability 
of the study results.  These pre-defined parameters will be monitored during the study.  
Important deviations from the QTL threshold limits for these parameters and remedial 
actions taken will be summarized in the clinical study report. 
Retention of study documents will be governed by the Clinical Trial Agreement. 
Case report forms (CRF) must be completed in English.  TRADENAMES® (if used) for 
concomitant medications may be entered in the local language.  Consult the country-
specific language requirements. 
All written information and other material to be used by subjects and investigative staff 
must use vocabulary and language that are clearly understood. 

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Source Documents 
The investigator is to maintain a list of appropriately qualified persons to whom he/she 
has delegated study duties.  All persons authorized to make entries and/or corrections 
on CRFs will be included on the Amgen Delegation of Authority Form. 
Source documents provide evidence for the existence of the subject and substantiate 
9-*.39*,7.9>4+9-*)&9&(411*(9*)"4:7(*)4(:2*398&7*+.1*)&99-*.3;*89.,&947H88.9* 
"4:7(*)4(:2*398&7*47.,.3&1)4(:2*398)&9&&3)7*(47)8+742<-.(-9-*8:'/*(9H8
CRF data are obtained.  These include but are not limited to hospital records, clinical 
and office charts, laboratory and pharmacy records, diaries, microfiches, radiographs, 
and correspondence.  Source documents may also include data captured in the IRT 
system (if used, such as subject ID and randomization number) and CRF entries if the 
CRF is the site of the original recording (ie, there is no other written or electronic record 
of data, such as paper questionnaires for a clinical outcome assessment or certain 
demographic information, such as gender, race, and ethnicity). 
Data reported on the CRF or entered in the electronic CRF 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 Investigator and study staff are responsible for maintaining a comprehensive and 
centralized filing system of all study-related (essential) documentation, suitable for 
inspection at any time by representatives from Amgen and/or applicable regulatory 
authorities. 
 
Subject files containing completed electronic CRF, informed consent forms, and 
subject identification list 
 
Study files containing the prot4(41<.9-&11&2*3)2*3983;*89.,&947H874(-:7*
copies of pre-study documentation, and all correspondence to and from the IRB/IEC 
and Amgen 
 
Investigational product-related correspondence including [Proof of Receipts, 
Investigational Product Accountability Record(s), Return of Investigational Product 
for Destruction Form(s), Final Investigational Product Reconciliation Statement, as 
applicable 
 
Non-investigational product(s), and/or medical device(s) or combination product(s) 
documentation, as applicable 
Retention of study documents will be governed by the Clinical Trial Agreement. 

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Remote Source Data Review and Verification 
If permitted by national and/or local regulations, remote Source Data Review and 
Verification (rSDR/V) can be implemented.  The clinical monitor should be provided with 
a secure, read-only access to the Electronic Medical Record (EMR) system, including all 
modules relevant for review.  This access should be restricted to the records of only 
those patients who participate in the trial and who did not object to remote access to 
their medical records.  A list of the monitors to whom remote access has been granted 
should be maintained.  In order to prevent unauthorized access, access rights should be 
revoked once rSDR/V tasks have been completed for the trial.  The EMR system should 
have an audit trail and be able to log information on who accessed data and when.  
Remote access to the EMR should only be possible using a two-factor authentication. 
Study and Site Closure 
Amgen or its designee may stop the study or study site participation in the study for 
medical, safety, regulatory, administrative, or other reasons consistent with applicable 
laws, regulations, and GCP.  
Both Amgen and the Investigator reserve the right to terminate th*3;*89.,&947H8
participation in the study according to the Clinical Trial Agreement.  The investigator is to 
notify the IRB/IEC .3<7.9.3,4+9-*89:)>H8(4251*9.4347*&71>9*72.3&9.43&3)8*3)&
copy of the notification to Amgen. 
Subjects may be eligible for continued treatment with Amgen investigational product(s) 
'>&8*5&7&9*57494(4147&8574;.)*)+47'>9-*14(&1(4:397>H87*,:1&947>2*(-&3.82
However, Amgen reserves the unilateral right, at its sole discretion, to determine 
whether to supply Amgen investigational product(s) and by what mechanism, after 
termination of the study and before the product(s) is/are available commercially. 
Compensation 
Any arrangements for compensation to subjects for injury or illness that arises in the 
study are described in the Compensation for Injury section of the Informed Consent that 
is available as a separate document. 
 

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11.4 
Appendix 4.  Safety Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up and Reporting 
Definition of Adverse Event 
Adverse Event Definition 
 
An adverse event is any untoward medical occurrence in a clinical study subject 
irrespective of a causal relationship with the study treatment.   
 
Note:  An adverse event can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or 
exacerbated) temporally associated with the use of a treatment, combination 
product, medical device or procedure. 
 
Note:  Treatment-emergent adverse events will be defined in the statistical 
analysis plan (SAP). 
 
Events Meeting the Adverse Event Definition 
 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, electrocardiogram, radiological scans, vital signs 
measurements), including those that worsen from baseline, that are considered 
clinically significant in the medical and scientific judgment of the investigator (ie, 
not related to progression of underlying disease). 
 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
 
New conditions detected or diagnosed after study treatment administration even 
though it may have been present before the start of the study. 
 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
 
Signs, symptoms, or the clinical sequelae of a suspected intentional overdose of 
either study treatment or a concomitant medication. Intentional overdose will be 
reported as an adverse event/serious adverse event when it is taken with possible 
suicidal/self-harming intent. Such intentional overdoses are to be reported 
regardless of sequelae. Accidental/unintentional overdose will be captured as a 
medication error.  
 
 E&(04+*++.(&(>F47E+&.1:7*4+*=5*(9*)5-&72&(414,.(&1&(9.43F5*78*<.11349'*
reported as an adverse event or serious adverse event.  Such instances will be 
captured in the efficacy assessments.  However, the signs, symptoms, and/or 
clinical sequelae resulting from lack of efficacy will be reported as adverse event or 
serious adverse event if they fulfill the definition of an adverse event or serious 
adverse event.   
 
Events NOT Meeting the Adverse Event Definition 
 
Medical or surgical procedure (eg, endoscopy, appendectomy):  the condition that 
leads to the procedure is the adverse event. 
 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 

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Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
Definition of Serious Adverse Event 
A Serious Adverse Event is defined as any untoward medical occurrence that, 
meets at least 1 of the following serious criteria: 
Results in death (fatal) 
Immediately life-threatening 
#-*9*72E1.+*-9-7*&9*3.3,F.39-*)*+.3.9.434+E8*7.4:8F7*+*7894&3*;*39.3<-.(-9-*
subject 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. 
Requires in-patient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the subject has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
&3)4797*&92*399-&9<4:1)349-&;*'**3&557457.&9*.39-*5->8.(.&3H84++.(*47
outpatient setting.  Complications that occur during hospitalization are an adverse 
event.  If a complication prolongs hospitalization or fulfills any other serious criteria, 
9-**;*39.88*7.4:8%-*3.3)4:'9&894<-*9-*7E-485.9&1.?&9.43F4((:77*)47<&8
necessary, the adverse event is to be considered serious.  Hospitalization for elective 
treatment of a pre-existing condition that did not worsen from baseline is not 
considered an adverse event. 
Results in persistent or significant disability/incapacity 
#-*9*72).8&'.1.9>2*&38&8:'89&39.&1).87:59.434+&5*7843H8&'.1.9>94(43):(9
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 (eg, sprained ankle) which may interfere 
with or prevent everyday life functions but do not constitute a substantial disruption. 
Is a congenital anomaly/birth defect 
Other medically important serious event 
Medical or scientific judgment is to be exercised in deciding whether serious adverse 
event 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 subject or may require medical or surgical intervention to prevent 1 of 

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the other outcomes listed in the above definition.  These events are typically to be 
considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse. 
 
Recording Adverse Events and Serious Adverse Events 
Adverse Event and Serious Adverse Event Recording 
 
When an adverse event or serious adverse event occurs, it is the responsibility of 
the investigator to review all documentation (eg, hospital progress notes, 
laboratory, and diagnostics reports) related to the event. 
 
The investigator will then record all relevant adverse event/serious adverse event 
information in the Event case report form (CRF). 
 
The investigator must assign the following mandatory adverse event attributes: 
o Adverse event diagnosis or syndrome(s), if known (if not known, signs or 
symptoms); 
o Dates of onset and resolution (if resolved); 
o Did the event start prior to first dose of investigational product; 
o Assessment of seriousness; 
o Severity (or toxicity defined below); 
o Assessment of relatedness to investigational product (efavaleukin 
alfa/placebo), other noninvestigational product(s)/auxiliary medicinal product(s), 
devices, and/or study-required activity and/or procedures; 
o Action taken; and 
o Outcome of event. 
 
If the severity of an adverse event changes from the date of onset to the date of 
resolution, record as a single event with the worst severity on the Event electronic 
CRF. 
 
9.8349&((*59&'1*+479-*.3;*89.,&947948*3)5-494(45.*84+9-*8:'/*(9H82*).(&1
records to sponsor/responsible contract research organization (CRO) in lieu of 
completion of the Event eCRF page. 
 
If specifically requested, the investigator may need to provide additional follow-up 
information, such as discharge summaries, medical records, or extracts from the 
medical records.  In this case, all subject identifiers, with the exception of the 
subject number, will be blinded on the copies of the medical records before 
submission to Amgen. 
 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  In such cases, the diagnosis (not the 

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individual signs/symptoms) will be documented as the adverse event/serious 
adverse event. 
Evaluating Adverse Events and Serious Adverse Events 
Assessment of Severity 
The investigator will make an assessment of severity for each adverse event and 
serious adverse event reported during the study.  The assessment of severity will be 
based on: 
The Common Terminology Criteria for Adverse Events, version 5 which is available at 
the following location:  
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
 
Assessment of Causality 
 
The investigator is obligated to assess the relationship between investigational 
product(s), noninvestigational product(s)/auxiliary medicinal product(s) , device(s), 
and/or study-required activity and/or procedure(s) and each occurrence of each 
adverse event/serious adverse event. 
 
Relatedness means that there are facts or reasons to support a relationship 
between investigational product and the event. 
 
The investigator will use clinical judgment to determine the relationship. 
 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study treatment 
administration will be considered and investigated. 
 
#-*.3;*89.,&947<.11&184(438:199-*3;*89.,&947H874(-:7*and/or Product 
Information, for marketed products, in his/her assessment. 
 
For each adverse event/serious adverse event, the investigator must document in 
the medical notes that he/she has reviewed the adverse event/serious adverse 
event and has provided an assessment of causality.  For sites reporting serious 
adverse events via electronic data capture (EDC), the investigator or sub 
investigator must confirm causality in EDC within 72 hours of the serious adverse 
event being entered on the Events CRF. 
 
There may be situations in which a serious adverse event has occurred and the 
investigator has minimal information to include in the initial report.  However, it is 
very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the serious adverse event data. 
 
The investigator may change his/her opinion of causality in light of follow-up 
information and send a serious adverse event follow-up report with the updated 
causality assessment.  In this case, for sites reporting serious adverse events via 
EDC, the investigator or sub-investigator must reconfirm causality in the EDC 
system within 72 hours of the serious adverse event being entered on the Events 
CRF. 

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The causality assessment is 1 of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of Adverse Event and Serious Adverse Event 
 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by 
Amgen to elucidate the nature and/or causality of the adverse event or serious 
adverse event as fully as possible.  This may include additional laboratory tests or 
investigations, histopathological examinations, or consultation with other health 
care professionals. 
 
If a subject is permanently withdrawn from protocol-required therapies because of 
a serious adverse event, this information must be submitted to Amgen. 
 
If a subject dies during participation in the study or during a recognized follow-up 
period, the investigator will provide Amgen with a copy of any post-mortem 
findings including histopathology. 
 
New or updated information will be recorded in the originally completed Event 
eCRF. 
 
The investigator will submit any updated serious adverse event data to Amgen 
immediately and no later than 24 hours of receipt of the information. 
Reporting of Serious Adverse Event 
Serious Adverse Event Reporting via Electronic Data Collection Tool 
 
The primary mechanism for reporting serious adverse event will be the electronic 
data capture (EDC) system. 
 
If the EDC system is unavailable, then the site will report the information to Amgen 
using a paper-based Serious Adverse Event Contingency Report Form (also 
referred to as the electronic Serious Adverse Event [eSAE] Contingency Report 
Form) (see 
) immediately and no later than 24 hours of the 
.3;*89.,&947H8&<&7*3*884+9-**;*39 
 
The site will enter the serious adverse event data into the electronic system as 
soon as it becomes available. 
 
After the study is completed at a given site, the EDC system 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 serious adverse event from a study subject or 
receives updated data on a previously reported serious adverse event after the 
EDC system has been taken off-line, then the site can report this information on 
the paper-based Serious Adverse Event Contingency Report Form (see 
 
 
 
Once the study has ended, serious adverse event(s) suspected to be related to 
investigational product will be reported to Amgen if the investigator becomes aware 
of a serious adverse event.  The investigator should use the paper-based Serious 
Adverse Event Contingency Report Form to report the event. 
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11.5 
Appendix 5.  Contraceptive Guidance and Collection of Pregnancy 
and Lactation Information 
Study-specific contraception requirements for females of childbearing potential are 
outlined in Section 5.2.  Contraceptive use and methods should be consistent with local 
regulations for subjects participating in clinical studies. 
Male and female subjects of childbearing potential should be advised of the pregnancy 
prevention requirements and the potential risk to the fetus if they become pregnant or 
father a child during treatment and for 6 weeks after the last dose of investigational 
product. 
Definition of Females of Childbearing Potential 
A female is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile.  Permanent sterilization methods include documented 
hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.  Females with 
documented permanent infertility due to an alternate medical cause (eg, Mullerian 
agenesis, androgen insensitivity, gonadal dysgenesis), can be considered not of 
childbearing potential. 
Note: Bilateral tubal ligation/occlusion is not considered a permanent sterilization 
method. 
Note:  Documentation from the following sources is acceptable to provide confirmation of 
*&(-89*7.1.?&9.432*9-4)7*;.*<4+8:'/*(9H82*).(&17*(47)8	8:'/*(9H82*).(&1
*=&2.3&9.4347
8:'/*(9H8medical history interview. 
A postmenopausal female is defined as: 
 
A woman of B55 years with no menses for 12 months without an alternative medical 
cause OR   
 
A woman age < 55 years with no menses for at least 12 months and with a 
follicle-89.2:1&9.3,-47243*"1*;*1<.9-.39-*)*+.3.9.434+E54892*345&:8&1
7&3,*F+479-*1&'47&947>.3;41;*)n the absence of 12 months of amenorrhea, 
confirmation with more than one FSH measurement is required. 
Contraception Methods for Female Subjects 
Highly Effective Contraceptive Methods 
 
Combined (estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation (oral, intravaginal, or transdermal) 
 
Progestogen-only hormonal contraception associated with inhibition of ovulation 
(oral, injectable, implantable) (except in Japan) 
 
Intrauterine device  
 
Intrauterine hormonal-releasing system  

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Bilateral tubal ligation/occlusion 
 
Vasectomized partner (provided that partner is the sole sexual partner of the female 
subject of childbearing potential and that the vasectomized partner has received 
medical assessment of the surgical success) 
 
Sexual abstinence (defined as refraining from heterosexual intercourse during the 
entire period of risk associated with the study treatments; the reliability of sexual 
abstinence must be evaluated in relation to the duration of the trial and the preferred 
and usual lifestyle of the subject) 
Collection of Pregnancy Information 
Female Subjects Who Become Pregnant 
 
Investigator will collect pregnancy information on any female subject who becomes 
pregnant while taking investigational product(s) and/or non-investigational 
product(s)/auxiliary medicinal product(s) through 6 weeks after last dose of 
investigational product. 
 
Information will be recorded on the Pregnancy Notification Form (see 
  
The form must be submitted to Amgen Global Patient Safety immediately and no 
later than 	-4:784+9-*8.9*H8&<&7*3*884+&8:'/*(9H857*,3&3(>49*".9*8&7*
not required to provide any information on the Pregnancy Notification Form that 
violates the country or regions local privacy laws). 
 
After obtaining the female 8:'/*(9H88.,3*)(438*39+477*1*&8*4+57*,3&3(>&3)
infant health information, the investigator will collect pregnancy and infant health 
information and complete the pregnancy questionnaire for any female subject who 
becomes pregnant while taking investigational product(s) and/or non-investigational 
product(s)/auxiliary medicinal product(s) through 6 weeks after the last dose of 
investigational product.  This information will be forwarded to Amgen Global Patient 
Safety.  Generally, infant follow-up will be conducted up to 12 months after the birth 
of the child (if applicable). 
 
Any termination of pregnancy will be reported to Amgen Global Patient Safety, 
regardless of fetal status (presence or absence of anomalies) or indication for 
procedure.  
 
While pregnancy itself is not considered to be an adverse event or serious adverse 
event, any pregnancy complication or elective termination of a pregnancy for medical 
reasons will be reported as an adverse event or serious adverse event.  Abnormal 
pregnancy outcomes (eg, spontaneous abortions, stillbirth, fetal death, congenital 
anomalies) will be reported as an adverse event or serious adverse event.  Note that 
an elective termination with no information on a fetal congenital malformation or 
maternal complication is generally not considered an adverse event, but still must be 
reported to Amgen as a pregnancy exposure case. 
 
Any serious adverse event occurring as a result of a post-study pregnancy which is 
considered reasonably related to the study treatment by the investigator, will be 
reported to Amgen Global Patient Safety as described in Section 11.4.  While the 
investigator is not obligated to actively seek this information in former study subjects, 
he or she may learn of a serious adverse event through spontaneous reporting.  
 
Any female subject who becomes pregnant while participating will discontinue 
investigational product while pregnant (see Section 7.1 for details). 
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Male Subjects with Partners Who Become Pregnant or Were Pregnant at the Time of 
Enrollment 
 
In the event a male subject fathers a child during treatment, and for an additional 
6 weeks after discontinuing investigational product(s) and/or noninvestigational 
product(s)/auxiliary medicinal product(s), the information will be recorded on the 
Pregnancy Notification Form.  The form (see
) must be submitted to 
Amgen Global Patient Safety immediately and no later than 24 -4:784+9-*8.9*H8
awareness of the pregnancy.  (Note: Sites are not required to provide any 
information on the Pregnancy Notification Form that violates the country or regions 
local privacy laws). 
 
The investigator will attempt to obtain a signed consent for release of pregnancy and 
infant health information directly from the pregnant female partner to obtain 
additional pregnancy information. 
 
+9*74'9&.3.3,9-*+*2&1*5&793*7H88.,3*)(438*39+477*1*&8*4+57*,3&3(>&3)
infant health information, the investigator will collect pregnancy outcome and infant 
health information on the pregnant partner and her baby and complete the 
pregnancy questionnaires.  This information will be forwarded to Amgen Global 
Patient Safety. 
 
Generally, infant follow-up will be conducted up to 12 months after the birth of the 
child (if applicable).  
 
Any termination of the pregnancy will be reported to Amgen Global Patient Safety 
regardless of fetal status (presence or absence of anomalies) or indication for 
procedure. 
Collection of Lactation Information 
 
Investigator will collect lactation information on any female subject who breastfeeds 
while taking investigational product(s) and/or noninvestigational product(s)/auxiliary 
medicinal product(s) through 6 weeks after the last dose of investigational product. 
 
Information will be recorded on the Lactation Notification Form (see below) and 
submitted to Amgen Global Patient Safety immediately and no later than 24 hours of 
9-*.3;*89.,&947H8&<&7*3*884f the event. 
 
Study treatment will be discontinued if female subject breastfeeds during the study 
as described in exclusion criterion 230. 
 
With the female subjects signed consent for release of mother and infant health 
information, the investigator will collect mother and infant health information and 
complete the lactation questionnaire on any female subject who breastfeeds while 
taking investigational product(s) and/or non-investigational product(s)/auxiliary 
medicinal product(s) through 6 weeks after discontinuing investigational product(s) 
and/or non-investigational product(s)/auxiliary medicinal product(s). 
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11.6 
Appendix 6.  Sample Storage and Destruction 
Any blood or tissue (eg, PK, biomarker) samples collected according to the Schedule of 
Activities can be analyzed for any of the tests outlined in the protocol and for any tests 
necessary to minimize risks to study subjects.  This includes testing to ensure analytical 
methods produce reliable and valid data throughout the course of the study.  This can 
also include, but is not limited to, investigation of unexpected results, incurred sample 
reanalysis, and analyses for method transfer and comparability.  
All samples and associated results will be coded prior to being shipped from the site for 
analysis or storage.  Samples will be tracked using a unique identifier that is assigned to 
the samples for the study.  Results are stored in a secure database to ensure 
confidentiality. 
If informed consent is provided by the subject, Amgen can do additional testing on 
remaining samples (ie, residual and back-up) to investigate and better understand the 
inflammatory conditions, the dose response and/or prediction of response to efavaleukin 
alfa, characterize antibody response, and characterize aspects of the molecule (eg, 
mechanism of action/target, metabolites).  Results from this analysis are to be 
documented and maintained, but are not necessarily reported as part of this study.  
Samples can be retained for up to 20 years. 
Since the evaluations are not expected to benefit the subject directly or to alter the 
treatment course, the results of pharmacogenetic, or other exploratory studies are not 
51&(*).39-*8:'/*(9H82*dical record and are not to be made available to the subject, 
members of the family, the personal physician, or other third parties, except as specified 
in the informed consent. 
The subject retains the right to request that the sample material be destroyed by 
contacting the investigator.  Following the request from the subject, the investigator is to 
provide the sponsor with the required study and subject number so that any remaining 
blood and tissue samples and any other components from the cells can be located and 
destroyed.  Samples will be destroyed once all protocol-defined procedures are 
completed.  However, information collected from samples prior to the request for 
destruction, will be retained by Amgen. 
The sponsor is the exclusive owner of any data, discoveries, or derivative materials from 
the sample materials and is responsible for the destruction of the sample(s) at the 
request of the subject through the investigator, at the end of the storage period, or as 

Product:  Efavaleukin Alfa 
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Page 113 of 131 
CONFIDENTIAL 
 
appropriate (eg, the scientific rationale for experimentation with a certain sample type no 
longer justifies keeping the sample).  If a commercial product is developed from this 
research project, the sponsor owns the commercial product.  The subject has no 
commercial rights to such product and has no commercial rights to the data, information, 
discoveries, or derivative materials gained or produced from the sample.  See 
Section 11.3 for subject confidentiality. 
 

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11.7 
Appendix 7.  Hepatotoxicity Stopping Rules:  Suggested Actions and 
Follow-up Assessments and Study Treatment Rechallenge 
Guidelines 
Subjects with abnormal hepatic laboratory values (ie, alkaline phosphatase [ALP], 
aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin [TBL]) 
and/or international normalized ratio (INR) and/or signs/symptoms of hepatitis (as 
described below) may meet the criteria for withholding or permanent discontinuation of 
Amgen investigational product or other protocol-required therapies, as specified in the 
Guidance for Industry Drug-Induced Liver Injury:  Premarketing Clinical Evaluation, 
July 2009. 
Criteria for Withholding and/or Permanent Discontinuation of Amgen 
Investigational Product and Other Protocol-required Therapies Due to Potential 
Hepatotoxicity 
The following stopping and/or withholding rules apply to subjects for whom another 
cause of their changes in liver biomarkers (TBL, INR and transaminases) has not been 
identified.  
Important alternative causes for elevated AST/ALT and/or TBL values include, but are 
not limited to: 
 
Hepatobiliary tract disease 
 
Viral hepatitis (eg, hepatitis A/B/C/D/E, Epstein-Barr Virus, cytomegalovirus, herpes 
simplex virus, varicella, toxoplasmosis, and parvovirus) 
 
Right sided heart failure, hypotension or any cause of hypoxia to the liver causing 
ischemia 
 
Exposure to hepatotoxic agents/drugs or hepatotoxins, including herbal and dietary 
supplements, plants and mushrooms 
 
Heritable disorders c&:8.3,.25&.7*),1:(:743.)&9.43*,.1'*79H88>3)742*
Crigler-Najjar syndrome) and drugs that inhibit bilirubin glucuronidation (eg, indinavir, 
atazanavir) 
 
Alpha-one antitrypsin deficiency 
 
Alcoholic hepatitis 
 
Autoimmune hepatitis 
 
%.1843H8).8*&8*&3)-*mochromatosis 
 
Nonalcoholic fatty liver disease including steatohepatitis 
 
Non-hepatic causes (eg, rhabdomyolysis, hemolysis) 
If investigational product(s) is/are withheld, the subject is to be followed for possible drug 
induced liver injury (DILI) according to recommendations in the last section of this 
appendix.  

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Rechallenge may be considered if an alternative cause for impaired liver tests (ALT, 
AST, ALP) and/or elevated TBL, is discovered and the laboratory abnormalities resolve 
to normal or baseline (see next section in this appendix). 
Table 11-3.  Conditions for Withholding and/or Permanent Discontinuation of 
Amgen Investigational Product and Other Protocol-required Therapies Due to 
Potential Hepatotoxicity 
Analyte 
Temporary Withholding 
Permanent Discontinuation 
TBL 
> 3x ULN  
at any time 
> 2x ULN 
 
 
OR 
INR 
-- 
> 1.5x (for subjects not on anticoagulation 
therapy) 
 
OR 
AND 
AST/ALT 
> 8x ULN at any time 
=$':9=$+47B	<**08 
> 5x ULN but < 8x ULN and unable to adhere 
to enhanced monitoring schedule 
> 3x ULN with clinical signs or symptoms that 
are consistent with hepatitis (such as right 
upper quadrant pain/tenderness, fever, 
nausea, vomiting, and jaundice) 
In the presence of no important alternative 
causes for elevated AST/ALT and/or TBL 
values 
> 3x ULN (when baseline was < ULN) 
 
OR 
ALP 
> 8x ULN at any time 
-- 
ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; INR = 
international normalized ratio; TBL = total bilirubin; ULN = upper limit of normal 
Criteria for Rechallenge of Amgen Investigational Product and Other 
Protocol-required Therapies After Potential Hepatotoxicity 
The decision to rechallenge the subject is to be discussed and agreed upon 
unanimously by the subject, investigator, and Amgen. 
If signs or symptoms recur with rechallenge, then efavaleukin alfa is to be permanently 
discontinued.  Subjects who clearly meet the criteria for permanent discontinuation (as 
described in Table 11-3) are never to be rechallenged. 
Drug-induced Liver Injury Reporting and Additional Assessments 
Reporting 
To facilitate appropriate monitoring for signals of DILI, cases of concurrent AST or ALT 
and TBL and/or INR elevation, according to the criteria specified in the above, require 
the following: 
 
The event is to be reported to Amgen as a serious adverse event within 24 hours of 
discovery or notification of the event (ie, before additional etiologic investigations 
have been concluded) 

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The appropriate Case Report Form (CRF) (eg, Events eCRF) that captures 
information necessary to facilitate the evaluation of treatment-emergent liver 
abnormalities is to be completed and sent to Amgen  
Other events of hepatotoxicity and potential DILI are to be reported as serious adverse 
events if they meet the criteria for a serious adverse event defined in Section 11.4. 
Additional Clinical Assessments and Observation 
All subjects in whom investigational product(s) or protocol-required therapies is/are 
withheld (either permanently or conditionally) due to potential DILI as specified in 
Table 11-3 or who experience AST or ALT elevations > 3 x upper limit of normal (ULN) 
or 2-fold increases above baseline values for subjects with elevated values before drug 
&7*94:3)*7,4&5*7.4)4+E(148*4'8*7;&9.43F:39.1&'3472&1.9.*87*9:73943472&14794
9-*8:'/*(9H8'&8*1.3*1*;*18 
Assessments that are to be performed during this period include:  
 
Repeat AST, ALT, ALP, bilirubin (BIL) (total and direct), and INR within 24 hours  
 
In cases of TBL > 2x ULN or INR > 1.5, retesting of liver tests, BIL (total and direct), 
and INR is to be performed every 24 hours until laboratory abnormalities improve 
Testing frequency of the above laboratory tests may decrease if the abnormalities 
stabilize or the investigational product(s) or protocol-required therapies has/have been 
discontinued AND the subject is asymptomatic. 
Initiate investigation of alternative causes for elevated AST or ALT and/or elevated TBL.  
The following are to be considered depending on the clinical situation: 
 
Complete blood count with differential to assess for eosinophilia 
 
Serum total immunoglobulin (Ig)G, anti-nuclear antibody anti-smooth muscle 
antibody, and liver kidney microsomal antibody-1 to assess for autoimmune hepatitis 
 
Serum acetaminophen (paracetamol) levels 
 
A more detailed history of:  
 
Prior and/or concurrent diseases or illness 
 
Exposure to environmental and/or industrial chemical agents  
 
Symptoms (if applicable) including right upper quadrant pain, hypersensitivity-
type reactions, fatigue, nausea, vomiting and fever 
 
Prior and/or concurrent use of alcohol, recreational drugs and special diets 
 
Concomitant use of medications (including non-prescription medicines and 
herbal and dietary supplements), plants, and mushrooms 
 
Viral serologies 
 
Creatine phosphokinase, haptoglobin, lactate dehydrogenase and peripheral blood 
smear 

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Appropriate liver imaging if clinically indicated 
 
Appropriate blood sampling for pharmacokinetic analysis if this has not already been 
collected 
 
Hepatology consult (liver biopsy may be considered in consultation with a 
hepatologist) 
Follow the subject and the laboratory tests (ALT, AST, TBL, INR) until all laboratory 
abnormalities return to baseline or normal or considered stable by the investigator.  The 
E(148*4'8*7;&9.435*7.4)F.894(439.3:*+47&2.3.2:24+ weeks after discontinuation 
of all investigational product(s) and protocol-required therapies. 
The potential DILI event and additional information such as medical history, concomitant 
medications and laboratory results must be captured in the corresponding eCRFs. 

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11.8 
Appendix 8.  Prohibited Medications 
This section outlines medications that are prohibited during the treatment phase of the 
study, including windows for prohibited medications prior to the screening endoscopy, if 
applicable. 
Drug Class 
Medication Restrictions 
Anti-TNF antibodies (eg, infliximab, 
adalimumab, golimumab)  
Discontinue at least 8 weeks prior to 
screening endoscopy and prohibited 
unless the subject has stopped 
investigational product permanently 
Anti-integrin antibodies (eg, 
vedolizumab) 
Discontinue at least 8 weeks prior to 
screening endoscopy and prohibited 
unless the subject has stopped 
investigational product permanently 
IL-12/23 antagonist (eg, ustekinumab) 
Discontinue at least 8 weeks prior to 
screening endoscopy and prohibited 
unless the subject has stopped 
investigational product permanently 
JAK inhibitors (eg, tofacitinib) 
Discontinue at least 4 weeks prior to 
screening endoscopy and prohibited 
unless the subject has stopped 
investigational product permanently 
S1P modulators (eg, ozanimod) 
Discontinue at least 4 weeks prior to 
screening endoscopy and prohibited 
unless the subject has stopped 
investigational product permanently 
Any other commercially approved 
biologic agent or targeted small molecule 
Discontinue at least 8 weeks prior to 
screening endoscopy or 5 half-lives prior 
to screening endoscopy, whichever is 
longer, and prohibited unless the subject 
has stopped investigational product 
permanently 
Immunomodulatory medications oral 
cyclosporine, intravenous cyclosporine, 
tacrolimus, sirolimus, mycophenolate 
mofetil, or thalidomide 
Discontinue at least 4 weeks prior to 
screening endoscopy and prohibited 
throughout duration of study 
Any investigational biologic therapy 
Discontinue at least 8 weeks prior to 
screening endoscopy or 5 half-lives prior 
to screening endoscopy, whichever is 
longer, and prohibited throughout 
duration of study 
Apheresis (eg, Adacolumn apheresis) 
Discontinue at least 2 weeks prior to 
screening endoscopy and prohibited 
throughout duration of study 

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T cell depleting agents (eg, 
antithymocyte globulin, Campath). 
Patients with exposure within 12 months 
prior to screening not eligible to be 
enrolled. 
Recombinant IL-2 (eg, Proleukin). 
Patients with any previous exposure not 
eligible to be enrolled. 
Corticosteroid enemas, corticosteroid 
suppositories, a course of IV 
corticosteroids or intramuscular 
corticosteroids, or oral budesonide 
standard formulation (not oral 
budesonide MMX) 
Discontinue at least 2 weeks prior to 
screening endoscopy and prohibited 
unless the subject has stopped 
investigational product permanently 
5-ASA enemas or 5-ASA suppositories 
Discontinue at least 2 weeks prior to 
screening endoscopy and prohibited 
unless the subject has stopped 
investigational product permanently 
Live vaccines 
Last vaccination (if any) given at least 5 
weeks prior to screening. Live vaccines 
are prohibited throughout the treatment 
period and for up to 6 weeks after the 
last dose of investigational product in the 
study. 
Any other investigational therapies or 
device 
Prohibited throughout duration of study. 
Abbreviations: 5-ASA = 5-aminosalicyclic acid; IL-2 = interleukin-2; IL-12/23 = interleukin 12/23; IV = 
intravenous; JAK = Janus Kinase; TNF = tumor necrosis factor; UC = ulcerative colitis. 
 

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11.9 
Appendix 9.  Permitted Medications 
This section outlines medications that are permitted during the treatment phase of the 
study, along with guidance for dose stabilization, if applicable. 
Drug Class 
Dose Stabilization Guidance 
Immunomodulators (eg, 6-MP, AZA, or 
methotrexate) 
Stable dose for 
 12 weeks prior to 
screening endoscopy. Doses should 
remain stable throughout study unless in 
9-*.3;*89.,&947H8(1.3.(&1/:),2*399-*8*
require discontinuation or dose 
reduction because of toxicity or other 
medical necessity; even if the toxicity 
resolves, the therapy must not be 
restarted. 
Oral 5-ASA compounds (eg, 
sulfasalazine, mesalamine) 
Stable dose for 
 2 weeks prior to 
screening endoscopy. Doses should 
remain stable throughout the induction 
period. Stable doses are encouraged 
during the long-term treatment period. 
Oral corticosteroids including 
budesonide (MMX) or beclomethasone 
dipropionate (gastro-resistant 
prolonged-release tablet) 
Stable dose for 
 2 weeks prior to 
screening endoscopy.  
For subjects in clinical response or 
clinical remission (as assessed at 
week 12), who are receiving oral 
corticosteroids upon entry into the 
long-term treatment period, the 
investigator must begin tapering the 
daily dose of corticosteroids at the week 
12 visit as described in 
Section 6.7.2.2.3. 
Antidiarrheals 
May continue during study with stable 
doses encouraged. 
Non-live vaccines 
Allowed during the study. 
Abbreviations: 5-ASA  5-aminosalicyclic acid; 6-MP  6-mercaptopurine; AZA  azathioprine 
 

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11.10 
Appendix 10.  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 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 

	 
Score 
Normal 
0 
Mild disease 
1 
Moderate disease 
2 
Severe disease 
3 
The total Mayo score is a composite index of 4 items (stool frequency, rectal bleeding, endoscopy findings, 
&3)5->8.(.&3H8,14'&1&88*882*39<.9-*&(-.9*2,7&)*)8*2.-quantitatively on a score of 0 to 3 for a 
maximal total score of 12.  Scores range from 0 to 12 points.  The Mayo Daily Symptom Diary will be used to 
record stool frequency and rectal bleeding. 
#-*24).+.*)&>48(47*.89-*&>48(47*<.9-4:99-*5->8.(.&3H8,14'&1&88*882*398:'8(47*&3)7&3,*8
from 0 to 9 points.  The modified Mayo score will be used to assess primary and secondary efficacy 
endpoints.  The partial Mayo score is the total Mayo score without the endoscopy subscore and ranges from 
0 to 9 points. 
The rectal bleeding and stool frequency subscores will be derived from the last 3 days of data entered within 
the last 7 days prior to the visit, or within 7 days prior to initiation of bowel preparations for visits which 
include an endoscopy.  The average score over the 3 days will be calculated using standard rounding rules. 

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11.11 
Appendix 11.  Country-specific Requirements 
This appendix provides language for country-specific regulatory requirements and other 
procedures to follow in the execution of the global study in these countries. 
The summary of changes outlined below specify requirements for sites and subjects 
participating in the European Union.  The country specific requirements for Japan will be 
outlined in a separate country specific supplement. 
Table 11-4.  EU Member States (Austria, Czech Republic, Italy, Poland, Germany, 
Hungary, Denmark, Finland, and Romania) Summary of Changes 
Protocol Section 
Text in Protocol 
Text For European Countries 
Section 4.1, Overall Design   
This phase 2 dose-finding 
study is a multicenter, 
randomized, double-blind, 
placebo-controlled, 
parallel-group, 12-week 
induction study of efavaleukin 
alfa in subjects with moderately 
to severely active UC who have 
failed at least 1 of the following: 
conventional therapy (eg, 
immunomodulators, 
corticosteroids), biologic 
therapy, or targeted small 
molecule (eg, JAK inhibitors).  
This study will be used to 
establish the efavaleukin alfa 
induction dose and 
maintenance dose/dosing 
regimens for continued 
development.  Subjects who 
complete the 12-week 
induction period will have the 
option to be treated in an 
exploratory long-term treatment 
period for up to 40 additional 
weeks if in the opinion of the 
investigator they may benefit 
from continued treatment.  The 
primary analysis will occur after 
all subjects have completed the 
week 12 visit or have early 
terminated.  All primary and 
secondary objectives will be 
evaluated at the primary 
analysis.  The objectives and 
endpoints for the study are 
defined in Section 3.  The 
overall study design is 
described by a study schema in 
Add: 
This phase 2 dose-finding study 
is a multicenter, randomized, 
double-blind, placebo-controlled, 
parallel-group, 12-week induction 
study of efavaleukin alfa in 
subjects with moderately to 
severely active UC who have 
failed at least 1 of the following: 
conventional therapy (eg, 
immunomodulators, 
corticosteroids), biologic therapy, 
or targeted small molecule (eg, 
JAK inhibitors).  This study will be 
used to establish the efavaleukin 
alfa induction dose and 
maintenance dose/dosing 
regimens for continued 
development (dosing decisions 
for further efavaleukin alfa 
development will not be based on 
one clinical efficacy endpoint 
alone but will include a 
comprehensive evaluation of all 
accumulated data, in particular 
safety and clinical 
pharmacology).  Subjects who 
complete the 12-week induction 
period will have the option to be 
treated in an exploratory 
long-term treatment period for up 
to 40 additional weeks if in the 
opinion of the investigator they 
may benefit from continued 
treatment.  The primary analysis 
will occur after all subjects have 
completed the week 12 visit or 
have early terminated.  All 
primary and secondary objectives 
will be evaluated at the primary 

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Protocol Section 
Text in Protocol 
Text For European Countries 
Section Study Schema 
1.2 (Figure 1-1). 
analysis.  The objectives and 
endpoints for the study are 
defined in Section 3.  The overall 
study design is described by a 
study schema in Section Study 
Schema 1.2 (Figure 1-1). 

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Protocol Section 
Text in Protocol 
Text For European Countries 
Section 4.3.2, Justification 
for Placebo 
 
Not applicable 
Add: 
4.3.2 Justification for Placebo 
It is important to have a placebo 
arm in order to evaluate both 
safety and efficacy of efavaleukin 
alfa, an investigational product in 
subjects with moderately to 
severely active UC.  Also, the 
inclusion of a placebo control arm 
is consistent with the principles 
outlined in International Council 
for Harmonization (ICH) E10 
(Note for guidance on choice of 
control group in clinical trials).  In 
addition, appropriate measures 
are in place for the safe medical 
supervision of subjects, and 
subjects have the right to 
withdraw from the study at any 
time and for any reason without 
prejudice to their future medical 
care by the physician or at the 
institution. 
Section 5.2, Exclusion 
Criteria, Disease Related, 
Criterion 202 
Replace: 
Criterion 202 
Disease limited to the rectum 
(ie, within 15 cm of the anal 
verge).   
With: 
Criterion 202 
Disease limited to the rectum.  
The investigator will need to 
assess each individual subject to 
determine if disease is limited to 
the rectum and appropriately 
exclude such subjects. 
Section 11.3, Appendix 3.  
Study Governance 
Considerations, Publication 
Policy, Paragraph 4 
 
Not applicable 
Add: 
Information on this study 
(2021-002537-41) and its results 
will be posted on the European 
Web site at 
www.clinicaltrialsregister.eu or on 
the European Union (EU) Clinical 
Trials Information System (CTIS), 
if applicable, no later than one 
year after the trial has ended. 

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Protocol Section 
Text in Protocol 
Text For European Countries 
Section 11.5, Appendix 5.  
Contraceptive Guidance 
and Collection of 
Pregnancy and Lactation 
Information, Definition of 
Females of Childbearing 
Potential, Paragraph 4 
Replace: 
A postmenopausal female is 
defined as: 
 
A woman of 
 55 years 
with no menses for 
12 months without an 
alternative medical cause 
OR   
 
A woman age  55 years 
with no menses for at least 
12 months and with a 
follicle-stimulating hormone 
(FSH) level within the 
definition of 
E54892*345&:8&17&3,*F
for the laboratory involved.  
In the absence of 
12 months of amenorrhea, 
confirmation with more 
than one FSH 
measurement is required. 
With: 
A postmenopausal state is 
defined as no menses for 
12 months without an alternative 
medical cause. A high follicle 
stimulating hormone (FSH) level 
in the postmenopausal range 
may be used to confirm a 
post-menopausal state in women 
not using hormonal contraception 
or hormonal replacement 
therapy.  However, in the 
absence of 12 months of 
amenorrhea, a single FSH 
measurement is insufficient. 
 

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Table 11-5.  Germany Summary of Changes 
Protocol Section 
Text in Protocol 
Text For Germany 
Section 4.1, Overall Design   
This phase 2 dose-finding 
study is a multicenter, 
randomized, double-blind, 
placebo-controlled, 
parallel-group, 12-week 
induction study of efavaleukin 
alfa in subjects with moderately 
to severely active UC who have 
failed at least 1 of the following: 
conventional therapy (eg, 
immunomodulators, 
corticosteroids), biologic 
therapy, or targeted small 
molecule (eg, JAK inhibitors).  
This study will be used to 
establish the efavaleukin alfa 
induction dose and 
maintenance dose/dosing 
regimens for continued 
development.  Subjects who 
complete the 12-week 
induction period will have the 
option to be treated in an 
exploratory long-term treatment 
period for up to 40 additional 
weeks if in the opinion of the 
investigator they may benefit 
from continued treatment.  The 
primary analysis will occur after 
all subjects have completed the 
week 12 visit or have early 
terminated.  All primary and 
secondary objectives will be 
evaluated at the primary 
analysis.  The objectives and 
endpoints for the study are 
defined in Section 3.  The 
overall study design is 
described by a study schema in 
Section Study Schema 1.2 
(Figure 1-1). 
Add: 
This phase 2 dose-finding study 
is a multicenter, randomized, 
double-blind, placebo-controlled, 
parallel-group, 12-week induction 
study of efavaleukin alfa in 
subjects with moderately to 
severely active UC who have 
failed at least 1 of the following: 
conventional therapy (eg, 
immunomodulators, 
corticosteroids), biologic therapy, 
or targeted small molecule (eg, 
JAK inhibitors).  This study will be 
used to establish the efavaleukin 
alfa induction dose and 
maintenance dose/dosing 
regimens for continued 
development (dosing decisions 
for further efavaleukin alfa 
development will not be based on 
one clinical efficacy endpoint 
alone but will include a 
comprehensive evaluation of all 
accumulated data, in particular 
safety and clinical 
pharmacology).  Subjects who 
complete the 12-week induction 
period will have the option to be 
treated in an exploratory 
long-term treatment period for up 
to 40 additional weeks if in the 
opinion of the investigator they 
may benefit from continued 
treatment.  The primary analysis 
will occur after all subjects have 
completed the week 12 visit or 
have early terminated.  All 
primary and secondary objectives 
will be evaluated at the primary 
analysis.  The objectives and 
endpoints for the study are 
defined in Section 3.  The overall 
study design is described by a 
study schema in 
Section Study Schema 1.2 
(Figure 1-1). 

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Protocol Section 
Text in Protocol 
Text For Germany 
Section 4.3.2, Justification 
for Placebo 
 
Not applicable 
Add: 
4.3.2 Justification for Placebo 
It is important to have a placebo 
arm in order to evaluate both 
safety and efficacy of efavaleukin 
alfa, an investigational therapy in 
subjects with moderately to 
severely active UC.  Also, the 
inclusion of a placebo control arm 
is consistent with the principles 
outlined in International Council 
for Harmonization (ICH) E10 
(Note for guidance on choice of 
control group in clinical trials).  In 
addition, appropriate measures 
are in place for the safe medical 
supervision of subjects, and 
subjects have the right to 
withdraw from the study at any 
time and for any reason without 
prejudice to their future medical 
care by the physician or at the 
institution.   

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Protocol Section 
Text in Protocol 
Text For Germany 
Section 5.2, Exclusion 
Criteria, Disease Related, 
Criterion 202 
Replace: 
Criterion 202 
Disease limited to the rectum 
(ie, within 15 cm of the anal 
verge).   
With: 
Criterion 202 
Disease limited to the rectum.  
The investigator will need to 
assess each individual subject to 
determine if disease is limited to 
the rectum and appropriately 
exclude such subjects.   
Section 7.1, Discontinuation 
of Study Treatment, 
Paragraph 1, Line 1 
 
Subjects (or a legally 
authorized representative) can 
decline to continue receiving 
investigational product and/or 
other protocol-required 
therapies and/or procedures at 
any time during the study but 
continue participation in the 
study. 
Delete (Strikethrough text only): 
Subjects (or a legally authorized 
representative) can decline to 
continue receiving investigational 
product and/or other 
protocol-required therapies 
and/or procedures at any time 
during the study but continue 
participation in the study. 
Section 8.2.1, Informed 
Consent 
 
All subjects or their legally 
authorized representative must 
sign and personally date the 
IRB/IEC and Amgen approved 
informed consent before any 
study-specific procedures are 
performed. 
Delete (Strikethrough text only): 
All subjects or their legally 
authorized representative must 
sign and personally date the 
IRB/IEC and Amgen approved 
informed consent before any 
study-specific procedures are 
performed. 
Section 11.3, Appendix 3.  
Study Governance 
Considerations, Informed 
Consent Process, 
Paragraphs 2, 3, 6, and 8 
 
The investigator or his/her 
delegated representative will 
explain to the subject, or their 
legally authorized 
representative, the aims, 
methods, anticipated benefits, 
and potential hazards of the 
study before any 
protocol-specific screening 
procedures or any 
investigational product(s) is/are 
administered, and answer all 
questions regarding the study. 
Delete (Strikethrough text only): 
The investigator or his/her 
delegated representative will 
explain to the subject, or their 
legally authorized representative, 
the aims, methods, anticipated 
benefits, and potential hazards of 
the study before any 
protocol-specific screening 
procedures or any investigational 
product(s) is/are administered, 
and answer all questions 
regarding the study. 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
Date:  21 August 2024 
Page 129 of 131 
CONFIDENTIAL 
 
Protocol Section 
Text in Protocol 
Text For Germany 
Section 11.3, Appendix 3.  
Study Governance 
Considerations, 
Informed Consent Process, 
Paragraphs 2, 3, 6, and 8 
(continued) 
(continued) 
Subjects must be informed that 
their participation is voluntary.  
Subjects or their legally 
authorized representative will 
then 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 
requirements, where 
applicable, and the IRB/IEC or 
study site. 
 
The acquisition of informed 
(438*39&3)9-*8:'/*(9H8
agreement or refusal of their 
notification of the primary care 
physician is to be documented 
.39-*8:'/*(9H82*).(&1
records, and the informed 
consent form is to be signed 
and personally dated by the 
subject or a legally authorized 
representative and by the 
person who conducted the 
informed consent discussion.  
Subject withdrawal of consent 
or discontinuation from study 
treatment and/or procedures 
must also be documented in 
9-*8:'/*(9H82*).(&17*(47)8
refer to Section 7. 
 
The original signed informed 
consent form is to be retained 
in accordance with institutional 
policy, and a copy of the 
informed consent form(s) must 
be provided to the subject or 
the 8:'/*(9H81*,&11>&:9-47.?*)
representative. 
Delete (Strikethrough text only): 
(continued) 
Subjects must be informed that 
their participation is voluntary.  
Subjects or their legally 
authorized representative will 
then 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 
requirements, where applicable, 
and the IRB/IEC or study site. 
 
 
 
The acquisition of informed 
consent and the s:'/*(9H8
agreement or refusal of their 
notification of the primary care 
physician is to be documented in 
9-*8:'/*(9H82*).(&17*(47)8
and the informed consent form is 
to be signed and personally 
dated by the subject or a legally 
authorized representative and by 
the person who conducted the 
informed consent discussion.  
Subject withdrawal of consent or 
discontinuation from study 
treatment and/or procedures 
must also be documented in the 
8:'/*(9H82*).(&17*(47)87*+*794
Section 7. 
 
 
The original signed informed 
consent form is to be retained in 
accordance with institutional 
policy, and a copy of the informed 
consent form(s) must be provided 
to the subject 479-*8:'/*(9H8
legally authorized representative. 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
Date:  21 August 2024 
Page 130 of 131 
CONFIDENTIAL 
 
Protocol Section 
Text in Protocol 
Text For Germany 
Section 11.3, Appendix 3.  
Study Governance 
Considerations, Publication 
Policy, Paragraph 4 
 
Not applicable 
Add: 
Information on this study 
(2021-002537-41) and its results 
will be posted on the European 
Web site at 
www.clinicaltrialsregister.eu or on 
the EU CTIS, if applicable, no 
later than one year after the trial 
has ended. 
Section 11.5, Appendix 5.  
Contraceptive Guidance 
and Collection of 
Pregnancy and Lactation 
Information, Definition of 
Females of Childbearing 
Potential, Paragraph 4 
Replace: 
A postmenopausal female is 
defined as: 
 
A woman of 
 55 years 
with no menses for 
12 months without an 
alternative medical cause 
OR   
 
A woman age  55 years 
with no menses for at least 
12 months and with a 
follicle-stimulating hormone 
(FSH) level within the 
definition of 
E54892*345&:8&17&3,*F
for the laboratory involved.  
In the absence of 
12 months of amenorrhea, 
confirmation with more 
than one FSH 
measurement is required. 
With: 
A postmenopausal state is 
defined as no menses for 
12 months without an alternative 
medical cause.  A high follicle 
stimulating hormone (FSH) level 
in the postmenopausal range 
may be used to confirm a 
post-menopausal state in women 
not using hormonal contraception 
or hormonal replacement 
therapy.  However, in the 
absence of 12 months of 
amenorrhea, a single FSH 
measurement is insufficient. 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
Date:  21 August 2024 
Page 131 of 131 
CONFIDENTIAL 
 
Table 11-6.  France Summary of Changes 
Protocol Section 
Text in Protocol 
Text for France 
Section 5.1, Inclusion 
Criteria, criterion 108 
 
Not Applicable 
Add: 
108 Subject affiliated to a social 
security scheme 
Section 5.2, Exclusion 
Criteria, Other Exclusions, 
criterion 238 (new) 
 
Not Applicable 
Add: 
238 Subjects falling under the 
vulnerable population (fetuses, 
neonates, pregnant women, 
children, prisoners, 
institutionalized individuals, adult 
subjects under legal protection 
measures [judicial protection or 
guardianship measures] or 
others who may be considered 
vulnerable) unless the subjects 
are illiterate or visually impaired. 
 

Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
Date:  21 August 2024 
 Page 1 of 2 
Superseding Amendment 4 
Protocol Title: A Phase 2, Dose-finding, Randomized, Double-blind, 
Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy 
of Efavaleukin Alfa Induction Therapy in Subjects with Moderately to 
Severely Active Ulcerative Colitis 
 
Amgen Protocol Number 20170104 
EudraCT Number 2021-002537-41 
NCT Number: Not Applicable  
 
Amendment Date: 
21 August 2024 
 
Rationale: 
This protocol is being amended to: 
 
To add the EU-CT number in response to EU requirements.

Product:  Efavaleukin Alfa 
Protocol Number:  20170104 
Date:  17 July 2024 
 Page 1 of 10 
Amendment 4 
Protocol Title: A Phase 2, Dose-finding, Randomized, Double blind, Placebo 
controlled, Multicenter Study to Evaluate the Safety and Efficacy of 
Efavaleukin Alfa Induction Therapy in Subjects with Moderately to Severely 
Active Ulcerative Colitis 
 
Amgen Protocol Number 20170104 
EudraCT Number 2021-002537-41 
NCT Number: Not Applicable  
 
Amendment Date: 
17 July 2024 
 
Rationale: 
This protocol is being amended to: 
 
Adjust number of subjects to 240 
 
Modify statistical considerations to match the new number of subjects 
 
Align language with newer protocol template

Product:  Efavaleukin alfa 
Protocol Number:  20170104 
Date:  04 May 2023 
Page 1 of 30 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
Amendment 3 
Protocol Title:  A Phase 2, Dose-finding, Randomized, Double-blind, 
Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of 
Efavaleukin Alfa Induction Therapy in Subjects with Moderately to Severely Active 
Ulcerative Colitis 
 
Amgen Protocol Number Efavaleukin Alfa 20170104 
EudraCT Number:  2021-002537-41 
 
Amendment Date: 
04 May 2023 
 
Rationale: 
This protocol is being amended to incorporate the following changes into the protocol: 
 
Updated overall design text to include an approximate number of subjects 
allowed to receive a biologic or targeted small molecule therapy and added a 
language to clarify that screening may be closed for subjects who are naïve to 
biologic or targeted small molecule therapy. 
 
Inclusion criteria was updated to remove the 20 years age requirement as the 
Taiwan civil code was amended and the adult age was changed from 20 to 
18 years. 
 
Inclusion criteria 104 was updated to align with regulatory guidance for clinical 
trials in population with moderately to severely active Ulcerative Colitis. 
 
Exclusion criteria was updated to clarify that subjects will be excluded if they 
receive live vaccines 5 weeks prior to screening, or plan to receive live vaccines 
during the treatment period and up to 6 weeks after the last dose of 
investigational product. 
 
Exclusion criteria was updated to clarify that subjects will be excluded if they 
have any active infection for which anti-infectives were indicated within 2 weeks 
(instead of 4 weeks) prior to screening. 
 
Included a new exclusion criterion to restrict female subjects to donate eggs 
during the study and also for 6 weeks after receiving the last dose of IP. 

Product:  Efavaleukin alfa 
Protocol Number:  20170104 
Date:  04 May 2023 
Page 2 of 30 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
 
Updated the excluded treatments, medical devices, and/or procedures during 
study period list to differentiate medications that are prohibited during the study 
and medications which are prohibited unless the subject has stopped 
investigational product permanently. 
 
Updated screening and enrollment requirement to specify that a subject must be 
randomized within a maximum of 35 days after the eligible screening endoscopy, 
including any rescreening period. 
 
A clarification was provided that if eligible screening assessments from previous 
screening periods may be used if the assessment was performed within 35 days 
prior to randomization. 
 
Included calculation for Mayo scores. 
 
Removed specification that hepatitis B DNA virus test details are not required for 
subjects with only HBsAg positive with everything else negative and history of 
vaccination and infection. 
 
Added Mayo Scoring System for the Assessment of Ulcerative Colitis Activity to 
the appendix. 
 
Included EEA country specific supplement within the protocol to specify changes 
that only apply to subjects in the EEA. 
 
Administrative, typographical, formatting, numbering, and abbreviation changes 
were made throughout the protocol. 

Product:  AMG 592 
Protocol Number:  20170104 
Date:  22 August 2022 
Page 1 of 2 
Amgen Proprietary - Confidential 
 
Superseded Amendment 2 
Protocol Title:  A Phase 2, Dose-finding, Randomized, Double blind, Placebo 
controlled, Multicenter Study to Evaluate the Safety and Efficacy of Efavaleukin 
Alfa Induction Therapy in Subjects with Moderately to Severely Active Ulcerative 
Colitis 
 
Amgen Protocol Number efavaleukin alfa 20170104  
 
Amendment Date: 
09 August 2022 
 
Superseded Amendment Date:  
 
22 August 2022 
 
Amendment Rationale: 
The rationale for this protocol amendment is: 
 
To add a third interim analysis (Section 9.4)  
 
To add information on subject participation in the long-term extension (LTE) 
study (20210210) (Schedule of Assessments, Sections 4.1.2, and 8.1.4)  
 
To clarify study procedures at the early termination and safety follow-up visits 
(Section 4.4, 8.1.4) 
 
To clarify language regarding endoscopy assessments to specify that  
colonoscopy can be performed instead of rectosigmoidoscopy when clinically 
indicated (Section 8.3.1).  In addition, “rectosigmoidoscopy” was changed to 
“endoscopy” throughout the document. 
 
To update prohibited and permitted concomitant medications (Section 5.1, 5.2, 
and 6.7) 
 
To update the dose justification section with recent data (Section 4.3.1) 
 
To incorporate changes for the European Union Clinical Trials Regulation (EU 
CTR) (Sections 1.1, 6.1, and 8.5.4) 

Product:  AMG 592 
Protocol Number:  20170104 
Date:  22 August 2022 
Page 2 of 2 
Amgen Proprietary - Confidential 
 
 
To consolidate the pharmacodynamics section and move it to a subsection of the  
biomarkers section.  Also, the biomarker discovery section was removed to 
reduce confusion (Section 8.8) 
 
To reduce the frequency of pregnancy testing (Section 1.3) 
 
To update safety reporting language (Section 8.5.4.1)  
 
To clarify population definitions for the statistical methods (Section 9.3)  
 
To update the DMC meeting schedule (Sections 1.1, 4.1, 9.4.1, and 11.3) 
 
Administrative and editorial updates. 
 
Superseded Amendment Rationale: 
 
To update benefit/risk information with recent data (Section 2.3). 
 

Product:  AMG 592 
Protocol Number:  20170104 
Date:  09 August 2022 
Page 1 of 2 
Amgen Proprietary - Confidential 
 
Amendment 2 
Protocol Title:  A Phase 2, Dose-finding, Randomized, Double blind, Placebo 
controlled, Multicenter Study to Evaluate the Safety and Efficacy of Efavaleukin 
Alfa Induction Therapy in Subjects with Moderately to Severely Active Ulcerative 
Colitis 
 
Amgen Protocol Number efavaleukin alfa 20170104  
 
Amendment Date: 
09 August 2022 
 
Amendment Rationale: 
The rationale for this protocol amendment is: 
 
To add a third interim analysis (Section 9.4)  
 
To add information on subject participation in the long-term extension (LTE) 
study (20210210) (Schedule of Assessments, Sections 4.1.2, and 8.1.4)  
 
To clarify study procedures at the early termination and safety follow-up visits 
(Section 4.4, 8.1.4) 
 
To clarify language regarding endoscopy assessments to specify that  
colonoscopy can be performed instead of rectosigmoidoscopy when clinically 
indicated (Section 8.3.1).  In addition, “rectosigmoidoscopy” was changed to 
“endoscopy” throughout the document. 
 
To update prohibited and permitted concomitant medications (Section 5.1, 5.2, 
and 6.7) 
 
To update the dose justification section with recent data (Section 4.3.1) 
 
To incorporate changes for the European Union Clinical Trials Regulation (EU 
CTR) (Sections 1.1, 6.1, and 8.5.4) 
 
To consolidate the pharmacodynamics section and move it to a subsection of the  
biomarkers section.  Also, the biomarker discovery section was removed to 
reduce confusion (Section 8.8) 
 
To reduce the frequency of pregnancy testing (Section 1.3) 

Product:  AMG 592 
Protocol Number:  20170104 
Date:  09 August 2022 
Page 2 of 2 
Amgen Proprietary - Confidential 
 
 
To update safety reporting language (Section 8.5.4.1)  
 
To clarify population definitions for the statistical methods (Section 9.3)  
 
To update the DMC meeting schedule (Sections 1.1, 4.1, 9.4.1, and 11.3) 
 
Administrative and editorial updates. 

Product:  Efavaleukin alfa 
Protocol Number:  20170104 
Date:  11 August 2021 
Page 1 of 1 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
Superseded Amendment 1 
Protocol Title:  A Phase 2, Dose-finding, Randomized, Double-blind, 
Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of 
Efavaleukin Alfa Induction Therapy in Subjects with Moderately to Severely Active 
Ulcerative Colitis 
 
Amgen Protocol Number efavaleukin alfa 20170104 
 
Amendment Date: 
 
Superseded Amendment Date: 
4 August 2021 
 
11 August 2021 
 
Amendment Rationale: 
 
To add hematology and chemistry laboratory assessments at week 2 of the induction 
period in the schedule of activities (Table 1-2) 
 
To add inclusion criteria age for subjects in Taiwan (Section 5.1) 
 
To add requirement for alternative therapy to reasons for early removal from 
protocol-required investigational product(s) (Section 7.1) 
 
To clarify language around inadequate response and disease worsening regarding 
subject discontinuation (Section 7.1) 
 
Administrative and editorial updates. 
 
Superseded Amendment Rationale: 
 
To change additional pregnancy testing from monthly to 
 (Section 1.3 
and Section 8.4.4.6) 
 
To add the unblinding of treatment assignment will be performed via IRT 
(Section 6.4.2.1) 
 

Product:  Efavaleukin alfa 
Protocol Number:  20170104 
Date:  4 August 2021 
Page 1 of 1 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
Amendment 1 
Protocol Title:  A Phase 2, Dose-finding, Randomized, Double-blind, 
Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of 
Efavaleukin Alfa Induction Therapy in Subjects with Moderately to Severely Active 
Ulcerative Colitis 
 
Amgen Protocol Number efavaleukin alfa 20170104 
 
Amendment Date: 
4 August 2021 
 
Rationale: 
The rationale for this protocol amendment is: 
 
To add hematology and chemistry laboratory assessments at week 2 of the induction 
period in the schedule of activities (Table 1-2) 
 
To add inclusion criteria age for subjects in Taiwan (Section 5.1) 
 
To add requirement for alternative therapy to reasons for early removal from 
protocol-required investigational product(s) (Section 7.1) 
 
To clarify language around inadequate response and disease worsening regarding 
subject discontinuation (Section 7.1) 
 
Administrative and editorial updates. 
 
 

Approval Signatures
Document Name:
Protocol Amendment efavaleukin alfa 20170104 superseding 4
Document Description:
Protocol Amendment #4
Document Number:
CLIN-000252783
Approval Date:
22 Aug 2024
Type of Study Protocol:
Amendment
Protocol Amendment No.: superseding 4
Document Approvals
Reason for Signing: Management
Name: 
Date of Signature: 22-Aug-2024 00:13:38 GMT+0000