A Phase 3, Multicenter, Randomized, Double-Blind, Parallel, Placebo-Controlled Induction Study of Mirikizumab in Conventional-Failed and Biologic-Failed Patients With Moderately to Severely Active Ulcerative Colitis (LUCENT 1)
Phase: PHASE3
Conditions: Ulcerative Colitis
Sponsor: Eli Lilly and Company

Protocol Addendum I6T-MC-AMAN (5) 
 
A Phase 3, Multicenter, Randomized, Double-Blind, Parallel, Placebo-Controlled Induction 
Study of Mirikizumab in Conventional-Failed and Biologic-Failed Patients with Moderately to 
Severely Active Ulcerative Colitis: Maximized Extended Enrollment Addendum 
 
NCT03518086  
 
Approval Date: 19-Mar-2018 
 
 

I6T-MC-AMAN(5) Maximized Extended Enrollment Protocol Addendum
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1. Protocol Addendum I6T-MC-AMAN(5)
A Phase 3, Multicenter, Randomized, Double-Blind, Parallel, 
Placebo-Controlled Induction Study of Mirikizumab in 
Conventional-Failed and Biologic-Failed Patients with 
Moderately to Severely Active Ulcerative Colitis: 
Maximized Extended Enrollment Addendum
Confidential Information
The information contained in this document is confidential and is intended for the use of 
clinical investigators.  It is the property of Eli Lilly and Company or its subsidiaries and 
should not be copied by or distributed to persons not involved in the clinical investigation of 
mirikizumab (LY3074828), unless such persons are bound by a confidentiality agreement 
with Eli Lilly and Company or its subsidiaries.   
Note to Regulatory Authorities:  This document may contain protected personal data 
and/or commercially confidential information exempt from public disclosure.  Eli Lilly and 
Company requests consultation regarding release/redaction prior to any public release.  In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.
Mirikizumab (LY3074828)
This addendum is to be performed in addition to all procedures required by protocol 
I6T-MC-AMAN or any subsequent amendments to that protocol.
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Addendum(5) Electronically Signed and Approved by Lilly on date provided 
below.
Approval Date: 19-Mar-2018 GMT

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2. Table of Contents
Protocol Addendum I6T-MC-AMAN (5)
A Phase 3, Multicenter, Randomized, Double-Blind, Parallel, 
Placebo-Controlled Induction Study of Mirikizumab in 
Conventional-Failed and Biologic-Failed Patients with 
Moderately to Severely Active Ulcerative Colitis: 
Maximized Extended Enrollment Addendum
Section
Page
1.
Protocol Addendum I6T-MC-AMAN(5) A Phase 3, Multicenter, 
Randomized, Double-Blind, Parallel, Placebo-Controlled Induction 
Study of Mirikizumab in Conventional-Failed and Biologic-Failed 
Patients with Moderately to Severely Active Ulcerative Colitis:  
Maximized Extended Enrollment Addendum......................................................................1
2.
Table of Contents................................................................................................................2
3.
Rationale for Addendum .....................................................................................................4
4.
Protocol Additions ..............................................................................................................5
4.1.
Extended Enrollment......................................................................................................5
4.2.
Investigational Plan........................................................................................................5
4.3.
Discontinuation of Study in Extended Enrollment Phase ................................................5
4.4.
Statistical and Analytical Plans.......................................................................................6
4.4.1.
Determination of Sample Size................................................................................6
4.4.2.
Statistical and Analytical Plans...............................................................................6
4.4.2.1.
General Considerations.....................................................................................6
4.4.2.2.
Interim Analyses...............................................................................................6

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List of Figures
Figure
Page
Figure AMAN(5).1.
Milestones for Global and ME2 Cohort enrollment through 
global and local submissions............................................................................5

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3. Rationale for Addendum
Regulatory agencies of some countries require local patient data from a specific number of 
patients for registration in their countries.  This addendum provides a mechanism to meet these 
country-level registration requirements in a single pivotal study.
The purpose of this addendum is to enable patient enrollment to continue in these countries if the 
prespecified number of patients from the respective countries cannot be enrolled in the main 
protocol (Study I6T-MC-AMAN [AMAN]).  Hereafter, patients enrolled in the main protocol 
will be referred to as the Global Cohort, and patients enrolled under the extended enrollment 
addendum will be referred to as the Maximized Extended Enrollment (ME2) Cohort.  The 
number of patients enrolled in the ME2 Cohort will depend on the local guidelines and the 
number of patients from those countries already enrolled in the Global Cohort.

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4. Protocol Additions
4.1.
Extended Enrollment
Once the protocol milestone of last-patient-enters-treatment (LPET) for the Global Cohort is 
reached, enrollment will continue for those countries participating in the ME2 cohort, if needed, 
until sufficient numbers of patients are enrolled to meet the regulatory needs for those countries.
Enrollment in the Global Cohort from the respective country is required before enrolling patients 
in the ME2 Cohort from the same country.
Figure AMAN(5).1 shows the milestones for enrollment in Study AMAN (Global Cohort and 
ME2 Cohort) through global and local submissions.
Abbreviations:  DBL = database lock; EU = European Union; FPV = first patient visit; 
LPET = last patient entered treatment; LPV = last patient visit; ME2 = Maximized 
Extended Enrollment; US = United States. 
Figure AMAN(5).1.
Milestones for Global and ME2 Cohort enrollment through global 
and local submissions.
4.2.
Investigational Plan
The objectives, enrollment criteria, randomization ratio, treatment, and evaluations of 
risk/benefit for patients enrolled in the ME2 Cohort will be identical to those for patients 
enrolled in the Global Cohort from these countries, including both those described in the main 
protocol, as well as in any applicable protocol addenda.
4.3.
Discontinuation of Study in Extended Enrollment Phase
Enrollment in the ME2 Cohort will be discontinued if results from the Global Cohort 
demonstrate futility, lack of efficacy, and/or an unacceptable safety profile.

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4.4.
Statistical and Analytical Plans
4.4.1. Determination of Sample Size
The total number of patients enrolled in each country is based on the minimum number of 
patients needed to support local registration.  The number of patients enrolled in the ME2 Cohort 
is dependent on the number of patients enrolled from each of the respective countries in Global 
Cohort as part of the protocol-defined sample size of 1160 patients. If a country fully meets
patient enrollment needs in the Global Cohort, no patient will be enrolled under this addendum 
for that country.
4.4.2. Statistical and Analytical Plans
4.4.2.1.
General Considerations
The benefit/risk profile to support global registrations will be based on the safety and efficacy 
analyses of Global Cohort.  Patients enrolled in the ME2 Cohort will not be included in the 
primary global analysis, as described in the statistical methods outlined in the main protocol of 
Study AMAN.  
Patients enrolled in the ME2 Cohort will be analyzed separately using the statistical 
methodology described in the main protocol of Study AMAN.  The data from the ME2 Cohort 
will be used in the respective countries to demonstrate similarity between local patients and the 
intent to treat (ITT) population enrolled in the Global Cohort.  Patients in the ME2 Cohort (and 
their investigators) will remain blinded until the ME2 Cohort is locked and unblinded.
As necessary, country-specific efficacy and safety analyses will be summarized for enrolled 
patients from each of the participating countries by pooling each country’s patients from the 
Global Cohort and the ME2 Cohort.  All analyses will be for descriptive purposes only.  Details 
of the analyses are described in the statistical analysis plan.
4.4.2.2.
Interim Analyses
No interim analyses are planned for the ME2 Cohort.

Leo Document ID = a6acf895-ab55-4624-9612-4f848da2b73a
Approver: 
Approval Date & Time: 19-Mar-2018 15:42:35 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 19-Mar-2018 15:42:35 GMT
Signature meaning: Approved
PPD
PPD