A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Efficacy and Safety of Mirikizumab to Secukinumab and Placebo in Patients With Moderate-to-Severe Plaque Psoriasis OASIS-2
Phase: PHASE3
Conditions: Psoriasis
Sponsor: Eli Lilly and Company

 
I6T-MC-AMAJ(1.1) Clinical Protocol Addendum 
 
 
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Efficacy 
and Safety of Mirikizumab to Secukinumab and Placebo in Patients with Moderate-to-Severe 
Plaque Psoriasis (OASIS-2) 
 
NCT03535194 
 
 Date: 26-Apr-2018 
 
 

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1. Protocol Addendum I6T-MC-AMAJ(1.1)
A Multicenter, Randomized, Double-Blind, Placebo-
Controlled Study Comparing the Efficacy and Safety of 
Mirikizumab to Secukinumab and Placebo in Patients with 
Moderate-to-Severe Plaque Psoriasis
OASIS-2
Confidential Information
The information contained in this protocol addendum 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.  This document and 
its associated attachments are subject to United States Freedom of Information Act (FOIA) 
Exemption 4. 
Mirikizumab (LY3074828)
This addendum is to be performed in addition to all procedures required by protocol 
I6T-MC-AMAJ or any subsequent amendments to that protocol.
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Addendum (1) Electronically Signed and Approved by Lilly:  8 March 2018.
Revised Protocol Addendum(1.1) Electronically Signed and Approved by Lilly on date 
provided below.
Approval Date: 26-Apr-2018 GMT

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2. Table of Contents
Protocol Addendum I6T-MC-AMAJ(1.1)
A Multicenter, Randomized, Double-Blind, Placebo-
Controlled Study Comparing the Efficacy and Safety of 
Mirikizumab to Secukinumab and Placebo in Patients with 
Moderate-to-Severe Plaque Psoriasis
OASIS-2
Section
Page
1.
Protocol Addendum I6T-MC-AMAJ(1.1) A Multicenter, 
Randomized, Double-Blind, Placebo-Controlled Study Comparing 
the Efficacy and Safety of Mirikizumab to Secukinumab and Placebo 
in Patients with Moderate-to-Severe Plaque Psoriasis  OASIS-2 .........................................1
2.
Table of Contents................................................................................................................2
3.
Rationale for Addendum .....................................................................................................6
4.
Protocol Additions ..............................................................................................................8
4.1.
Section 2:  Schedule of Activities...................................................................................8
4.2.
Section 4:  Objectives and Endpoints............................................................................12
4.3.
Section 5:  Study Design ..............................................................................................12
4.4.
Section 6:  Study Population.........................................................................................15
4.5.
Section 7.7:  Concomitant Therapy...............................................................................17
4.6.
Section 8.2:  Discontinuation from the Study................................................................19
4.7.
Section 9:  Study Assessments and Procedures.............................................................19
4.8.
Section 10:  Statistical Considerations..........................................................................21
5.
References ........................................................................................................................23

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List of Tables
Table
Page
Table AMAJ(1).1.
Objectives and Endpoints..........................................................................12
Table AMAJ(1).2.
Excluded Classes of Concomitant Medications or Classes with 
Restricted Use ...............................................................................................18

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List of Figures
Figure
Page
Figure AMAJ(1).1.
Illustration of study design for Clinical Protocol I6T-MC-AMAJ 
addendum (1).................................................................................................14

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List of Attachments 
Attachment
Page
Attachment 1.
Protocol Addendum AMAJ(1) Clinical Laboratory Tests...............................24
Attachment 2.
Protocol Addendum Revisions.......................................................................25

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3. Rationale for Addendum
The following additions are being made to Protocol I6T-MC-AMAJ (AMAJ) for patients in 
Japan in order to conform with local requirements.  This addendum is to be performed in Japan 
in addition to all procedures required by this protocol or any subsequent amendments to this 
protocol.
This addendum enables the inclusion of patients with generalized pustular psoriasis (GPP) and 
erythrodermic psoriasis (EP).  These variants of psoriasis are relatively rare but can be more 
severe than chronic plaque psoriasis.  GPP is characterized by multiple sterile pustules all over 
the body and may be accompanied by systemic symptoms including fever, chills, severe itching, 
dehydration, rapid pulse rate, exhaustion, anemia, weight loss, and muscle weakness.  For this 
addendum, the eligibility criteria for GPP are set by the Japan Ministry of Health, Labour and 
Welfare (MHLW).  EP is a particular inflammatory type of psoriasis that can affect the whole 
body.  The reddening and shedding of the skin are often accompanied by severe itching and pain, 
heart rate increase, fluid loss, and fluctuating body temperature.  For this addendum, the 
eligibility criteria for EP are based on the accepted current medical practice (Takigawa et al. 
2010).  Both psoriasis subtypes can sometimes be life-threatening without adequate treatment.  
The treatment options available for severe plaque psoriasis have been used in both subtypes, but 
often these subtypes are refractory to existing therapies.  There are significant unmet medical 
needs for effective treatments for patients with GPP or EP.
Based on (1) postmarketing findings in Japanese patients with rheumatoid arthritis who were 
receiving anti-tumor necrosis factor (TNF) agents (Takeuchi et al. 2008; Koike et al. 2009), 
(2) recommendations set by the Japanese Dermatological Association for use of biologics in 
psoriasis (Ohtsuki et al. 2013), and (3) possible safety issues of Japanese patients with general 
autoimmune disease who received immunomodulators or immunosuppressants, the following 
additions are being made to Protocol AMAJ for patients in Japan:

Chest radiography will be performed:
o
at Week 52
o
for subjects who discontinue the study early, if more than 12 weeks have elapsed 
since the previous study radiography was obtained.  If medically indicated, this 
radiography may be performed even when 12 weeks have not elapsed since the 
previous study radiography
o
chest radiography may be performed at any time during the study, including the 
follow-up period, if medically necessary in the opinion of the investigator

Added explicit exclusion criteria and discontinuation criteria for patients with 
pneumocystis pneumonia (PCP) 

Added testing of serum beta-D-glucan levels (Tasaka et al. 2007)

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
Added testing of serum KL-6 levels

Discontinuation criterion added to discontinue patients who have any positive hepatitis B
deoxyribonucleic acid (HBV DNA) test at any time during the study

Modified HBV DNA monitoring for patients who are positive for anti-hepatitis B core 
antibody (HBcAb+) and/or positive for anti-hepatitis B surface antibody (HBsAb+) at 
screening

Exclusion criteria modified to permit the use of concomitant therapy for GPP and EP
All Japanese patients must participate in this addendum and must provide informed consent to 
the addendum.

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4. Protocol Additions
The added underlined text or strikethrough text in the following sections shows the changes 
applicable to patients participating in Study AMAJ in Japan.  Additionally, a list of additional 
clinical laboratory tests is provided in Attachment 1.
4.1.
Section 2:  Schedule of Activities

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Section 2:  Schedule of Activities
Procedurea
Screening 
Period
Baseline
Induction Period
Maintenance Period
Visit Number
V1b
V2
V3
V4
V5
V6
V7
V8
V9
V
10
V
11
V 
12
V 
13
V 
14
V
15
V
16
V 
17
V
18
Week
-4
0
1
2
3
4
8
12
16
20
24
28
32
36
40
44
48
52
Day with Visit 
Tolerance Interval
≤28 days 
from V2
1
8
± 3
15
± 3
22
± 3
29
± 3
57
± 5
85
± 5
113
± 5
141
± 5
169
± 5
197
± 5
225
± 5
253
± 5
281
± 5
309
± 5
337
± 5
365
± 5
Chest Radiography for 
TB Screeninge
Xe
X
Investigator 
Completed Clinical 
Efficacy Scales
Assessment of dermal 
symptoms
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Global improvement 
score
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Tests
HBV DNA testingn
X
X
X
X
X
X
X
X
X
X
X
X
Beta-D-glucan*
X
KL-6**
X

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Section 2:  Schedule of Activities
Procedurea
ETVs
Follow-up Periodt
Visit Number
V801
V802
Week 
LV+4W
LV+12W
Day with Visit Tolerance Interval
29
± 5
85
± 5
Chest Radiography for TB Screeninge
X
Investigator Completed Clinical 
Efficacy Scales
Assessment of dermal symptoms
X
Global improvement score
X
Laboratory Tests
HBV DNA testingn
X
X
X
Abbreviations:  DNA = deoxyribonucleic acid; ETV = early termination visit; HBcAb = anti-hepatitis B core antibody; HBsAb+ = hepatitis B surface antibody 
positive; HBV = hepatitis B virus; IP = investigational product; LV = last study visit; PCP = pneumocystis pneumonia; TB = tuberculosis; V = visit; 
W = weeks.
a
All activities should be completed prior to any study dose administration unless otherwise stated.
b
Visit 1 procedures may be conducted over more than 1 day as long as all tasks are completed within the allowable visit tolerance (at least 3 days should be 
allowed for receipt of laboratory test results).
e
Chest radiography will be performed locally at screening unless it has been performed within 3 months before initial screening (provided the radiographs 
and/or formal report are available for the investigator’s review).  In addition, chest radiography will be performed at Week 52, or for subjects who discontinue 
the study early if more than 12 weeks have elapsed since the previous study radiography was obtained.  This radiography may be performed within 12 weeks 
if medically indicated. In the opinion of the investigator, if evaluating chest radiography is medically necessary, the investigator may do so any time during 
the study, including the follow-up period.  For additional details, see revised Section 9.4.5.3 in Section 4.7 of the addendum.
n
Any enrolled patient who is HBcAb+ and/or HBsAb+ will undergo periodic monitoring of HBV DNA with HBV DNA testing (JSH 2017) (see revised
Section 9.4.5.4 in Section 4.7 of the addendum). Any patient with a positive HBV DNA test at any time must be discontinued from the study and receive 
appropriate follow-up medical care, including consideration for antiviral therapy.  (Refer to revised Section 9.4.5.4 in Section 4.7 of the addendum for further 
information regarding the timing of discontinuation).
s
If a patient discontinues IP early, the patient will complete the ETV and then enter the Post-Treatment Follow-up Period (V801 + V802).
t
All patients who receive IP but do not participate in Study I6T-MC-AMAH must enter the Follow-up Period and complete V801 + V802.
* Beta-D-glucan is required at screening and, if an investigator believes it is warranted, at subsequent visits; a beta-D-glucan test may be included in the work 
up panel at any time during the study, including in the follow-up period.  If the beta-D-glucan test is positive, PCP needs to be ruled out.  If PCP is ruled out 
and the investigator deems the patient fit to continue, the patient may continue in the study.  If a patient has a confirmed diagnosis of PCP during the study, 
the patient must discontinue the study.

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** KL-6 is required at screening and, if an investigator believes it is warranted, at subsequent visits; a KL-6 test may be included in the work-up panel at any 
time during the study, including in the follow-up period.

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4.2.
Section 4: Objectives and Endpoints
Objectives in the main protocol are not applied to GPP and EP patients. Selected endpoints in 
the main protocol are applied to GPP and EP patients. The following objectives and endpoints 
are added to the study as exploratory objectives:
Table AMAJ(1).1.
Objectives and Endpoints
Exploratory
To assess the efficacy of mirikizumab in patients 
with GPP.
GPP ONLY
Time course of response to treatment as measured by the 
following measures:

global improvement score

assessment of dermal symptoms for GPP

change from baseline in PASI

change from baseline in DLQI total score
At Week 16 and Week 52:

change from baseline in global improvement score

change from baseline in assessment of dermal 
symptoms for GPP

change from baseline in PASI

change from baseline in DLQI total score
To assess the efficacy of mirikizumab in patients 
with EP
EP ONLY
Time course of response to treatment as measured by the 
following measures:

global improvement score

change from baseline in PASI

change from baseline in DLQI total score
At Week 16 and Week 52:

global improvement score

change from baseline in PASI

change from baseline in DLQI total score
Abbreviations:  DLQI = Dermatology Life Quality Index; GPP = generalized pustular psoriasis; PASI = Psoriasis 
Area and Severity Index.
4.3.
Section 5: Study Design
5.1. Overall Design
Study I6T-MC-AMAJ is a Phase 3 multicenter, randomized, double-blind, placebo- and active-
controlled, parallel group, multi-period study in adult patients with moderate-to-severe plaque 
psoriasis.  Approximately 1443 patients will be randomized to treatment groups involving 

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different mirikizumab doses, placebo, or secukinumab. The study is comprised of 2 treatment 
periods (Induction, and Maintenance) which together lasts for up to 52 weeks, followed by a 12-
week Post-Treatment Follow-Up period. The main protocol for Study AMAJ will enroll patients 
with plaque psoriasis (Cohort 1). 
In parallel, the AMAJ(1) addendum will enroll Japanese patients who are diagnosed as GPP by 
the Japanese Dermatological Association or EP who have ≥80% body surface area (BSA)
involvement (with inflammatory erythema) (Cohort 2). Approximately 8 patients with GPP and 
8 patients with EP will be enrolled in Cohort 2 in Japan. During the Induction Period, GPP and 
EP patients will receive 250 mg mirikizumab subcutaneously (SC) at Weeks 0, 4, 8, and 12.  
During the Maintenance Period, starting at Week 16, GPP and EP patients will receive 250 mg 
mirikizumab every 8 weeks (Q8W) SC for up to a total of 52 weeks. Placebo control is not 
required for the GPP and EP patient arms because placebo-controlled studies are not ethical for 
patients with these severe conditions. The enrollment period of Cohort 2 will begin in parallel 
with the enrollment period of Cohort 1, but Cohort 2 enrollment may continue for a longer 
period of time if necessary to achieve the numbers planned for Cohort 2.
Figure AMAJ(1).1 illustrates the study design.  

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Abbreviations: EP = erythrodermic psoriasis; GPP = generalized pustular psoriasis; 
LV = last study visit; miri =mirikizumab; Q4W = every 4 weeks; Q8W = every 8 
weeks; V = visit; w = weeks; W = week.
* Option to enter Study AMAH or to enter the Post-Treatment Follow-Up Period.
Note: At Week 0 (V2), patients will be randomized in a 4:4:4:1 ratio to one of the 
following induction and maintenance period treatments:  a) 250 mg miri at Weeks 0, 4, 
8, 12 followed by 250 mg miri SC Q8W starting at Week 16; b) 250 mg miri at Weeks 
0, 4, 8, 12 followed by 125 mg miri Q8W starting at Week 16; c) 300 mg secukinumab
at Weeks 0, 1, 2, 3, 4, followed by 300 mg secukinumab Q4W starting at Week 4; d) 
placebo at Weeks 0, 4, 8, 12, followed by 250 mg miri Q4W starting at Week 16  
through Week 32 followed by Q8W thereafter. Patients will receive placebo to 
maintain the study blind across treatment groups.  Dosing is via subcutaneous injection 
(SC) for all treatments in all periods.
At Week 0 (V2), patients with GPP/EP will be assigned to 250 mg miri at Weeks 0, 4, 
8, 12, followed by 250 mg miri SC Q8W starting at Week 16.  Dosing is via SC 
injection for all treatments in all periods.
Figure AMAJ(1).1.
Illustration of study design for Clinical Protocol I6T-MC-AMAJ 
addendum (1).
Post-Treatment 
Follow-Up Period
Screening
Placebo Q4W
W0 to W12
Primary Endpoint
250 mg miri Q8W 
125 mg miri Q8W
300 mg 
secukinumab
W0, W1, W2, W3, 
W4, W8, W12
Induction
Period
Maintenance
Period
250 mg miri Q4W
W0 to W12
300 mg secukinumab Q4W
250 mg miri Q4W
at W16 to W32
W0
V2
W16
V9
W52
V18
LV+4w
V801
LV+12w
V802
W 4
V1
*
*
*
*
GPP/EP 
patients
250 mg miri
W0, W4, W8, W12
250 mg miri Q8W 
*
Plaque 
psoriasis 
patients
Cohort 2
AMAJ addendum
for Japan 
Cohort 1 
AMAJ 
protocol
250 mg miri Q8W
at W40 and W48

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4.4.
Section 6:  Study Population
6.1.  Inclusion Criteria
Type of Patient and Disease Characteristics
[1]
Present with chronic plaque psoriasis based on an investigator confirmed 
diagnosis of chronic psoriasis vulgaris for at least 6 months prior to baseline 
and meet the following criteria: 
A.
Plaque psoriasis involving 10% body surface area (BSA) and absolute 
PASI score 12 in affected skin at screening (Visit 1) and baseline 
(Visit 2), and
B.
sPGA score of 3 at screening (Visit 1) and baseline (Visit 2).
[2]
Candidate for systemic therapy and/or phototherapy
[36]
GPP ONLY: 
Meet the criteria for GPP set by the MHLW at screening (Visit 1) and baseline 
(Week 0; Visit 2).
[37]
EP ONLY:
Diagnosed to have BSA ≥80% involvement (with inflammatory erythema) at 
screening (Visit 1) and baseline (Week 0; Visit 2).
6.2.  Exclusion Criteria
[13]
Have hepatitis B or test positive for hepatitis B virus (HBV) at screening, defined as: 
A.
Positive for hepatitis B surface antigen (HBsAg+),
OR
B.
Positive for hepatitis B core antibody (HBcAb+) in conjunction with positive 
confirmatory HBV for HBV deoxyribonucleic acid (DNA) test,
OR
C.
Positive HBV DNA, regardless of anti-hepatitis B surface antibody (HBsAb) 
status.  Positive for hepatitis B surface antibody (HBsAb+) and positive 
confirmatory for HBV DNA
Note:  Patients who are HBcAb+ and/or HBsAb+ and HBV DNA negative 
may be enrolled in the study.  Patients who meet these criteria at screening 
will be monitored during the study as detailed in revised protocol 
Section 9.4.5.4 (Section 4.7 of this addendum).  

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[16]
Have had serious, opportunistic (see Section 9.2.3 and Appendix 4), or 
chronic/recurring infection (including pneumocystis pneumonia [PCP]) within 3 
months prior to screening.  Examples include, but are not limited to, infections 
requiring IV antibiotics, hospitalization, or prolonged treatment.
[23]
Have any other skin conditions (excluding plaque psoriasis, pustular psoriasis, and
erythrodermic psoriasis) that would affect interpretation of the results (including, 
but not limited to, scleroderma, eczema, drug-induced psoriasis, guttate psoriasis, 
pustular psoriasis, parapsoriasis, or cutaneous manifestations of other autoimmune 
diseases such as systemic lupus erythematosus).
Prior/Concomitant Therapy
[24]
Have received systemic nonbiologic therapy (including, but not limited to, oral 
psoralen plus ultraviolet A [PUVA] light therapy; cyclosporine; corticosteroids; 
methotrexate; oral retinoids; apremilast; tofacitinib; mycophenolate mofetil; 
thioguanine; hydroxyurea; sirolimus; tacrolimus; azathioprine; leflunomide; 
fumaric acid derivatives; or 1, 25 dihydroxy vitamin D3 and analogues) or 
phototherapy (including either oral and topical PUVA light therapy, ultraviolet B, 
excimer laser, or self treatment with tanning beds or therapeutic sunbathing) 
within 28 days prior to baseline.
[24a] GPP/EP ONLY:

Methotrexate or oral retinoids will be permitted before and during the study if 
doses are not greater than that of baseline.

Oral corticosteroids will be permitted before and during the study, if average 
daily doses are not greater than 10 mg/day of prednisone or its equivalent.

Cyclosporine will be permitted until Week 2 (Visit 4), if daily doses are not 
greater than that of baseline.
[25]
Have received topical treatment (including, but not limited to, corticosteroids [mild 
or least potent topical steroids will be permitted for use limited to the face, axilla, 
or genitalia], crisaborole, anthralin, calcipotriene, topical vitamin D derivatives, 
retinoids, tazarotene, pimecrolimus, tacrolimus, emollients and other 
nonprescription topical products containing urea, >3% salicylic acid, alpha- or 
beta-hydroxyl acids, or medicated shampoos [for example those that contain >3% 
salicylic acid, corticosteroids, coal tar, or vitamin D3 analogues]) within 14 days 
prior to baseline.
[25a] GPP/EP ONLY:

All topical treatment will be permitted before and during the study.
[28]
Have previous exposure to any biologic therapy targeting IL-12/23 (p40 subunit) 
or IL-23 (p19 subunit) or IL-17, either marketed or investigational.
[28a] GPP/EP ONLY:

Previous exposure targeting IL-17 is permitted before the study, unless the 
patient received anti-IL-17 targeting biologics within 12 weeks prior to baseline.

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Other Exclusions
[38]
Have a positive beta-D-glucan test at screening.
4.5.
Section 7.7:  Concomitant Therapy
All concomitant medications taken during the study must be recorded on the applicable
Concomitant Medication electronic case report form (eCRF).  All patients should maintain their 
usual medication regimens for concomitant conditions or diseases throughout the study unless 
those medications are specifically excluded in the protocol. 
Patients taking concomitant medications should be on stable dosages at the time of baseline and 
should remain at stable dosages throughout the study unless changes need to be made because of 
AEs.  
For patients with GPP or EP, methotrexate and oral retinoids will be permitted before and during 
the study if the patients have been using such medication before starting the study and if doses 
are not greater than that of baseline.  Oral corticosteroids will be permitted before and during the 
study, if the patients have been using such medication before starting the study and if average 
daily doses are not greater than 10 mg/day of prednisone or its equivalent.  Cyclosporine will be 
permitted until Week 2 (Visit 4), if the patients have been using such medication before starting 
the study and if daily doses are not greater than that of baseline.  For methotrexate, oral retinoids, 
oral corticosteroids and cyclosporine, dose reductions are allowed but dose increases of these 
drugs are not allowed during the study.  All topical treatment will be permitted before and during 
the study.
Additional systemic drugs are to be avoided during the study, unless required to treat AEs.  If the 
need for concomitant medication arises for an AE or for appropriate medical management 
(including the limited use of therapeutic agents which, if used under treatment regimens other 
than for treating an AE or for appropriate medical management, might be considered psoriasis 
therapies), the investigator should base decisions on the patient and clinical factors.  Other 
medications may be allowed if they are approved by the Sponsor or its designee.
Use of nonlive (killed, inactivated, or subunit) vaccinations are allowed for all patients; however, 
their efficacy with concomitant mirikizumab is unknown.  Use of live, attenuated vaccines are 
prohibited.  
Classes of therapies not permitted during the course of the study or permitted with use 
restrictions are specified in Table AMAJ(1).2 (see also the Exclusion Criteria [Section 6.2 of the 
protocol]):

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Table AMAJ(1).2.
Excluded Classes of Concomitant Medications or Classes with 
Restricted Use 
Drug Class
Allowed for 
Chronic Use 
Allowed with 
Restrictions
Conditions for Allowed Use
Topical treatment for psoriasis or any 
other skin condition 
(including but not limited to, 
corticosteroids, crisaborole, anthralin, 
calcipotriene, topical vitamin D 
derivatives, retinoids, tazarotene, 
pimecrolimus, tacrolimus, emollients 
and other nonprescription topical 
products containing urea, >3% salicylic 
acid, alpha- or beta-hydroxyl acids)
N
N
Exception:  For patients with GPP 
or EP, all topical treatments will be 
permitted.  These topical 
medications should not be used 
within approximately 12 hours 
prior to study visits.
Topical treatment for psoriasis limited to 
face, axilla, or genitalia
N
Y
Mild or least potent topical steroids 
will be permitted for use limited to 
the face, axilla, and/or genitalia, as 
needed.  These topical medications 
should not be used within 
approximately 24 hours prior to 
study visits.
Photochemotherapy 
(for example,PUVA)
N
N
Phototherapy 
(for example, UVA, UVB, excimer laser)
N
N
Biological immunomodulating agents
(for example, alefacept, briakinumab, 
efalizumab, ixekizumab, secukinumab, 
etanercept, adalimumab, infliximab, 
certolizuamb)
N
N
Other systemic immunomodulating 
treatments (for example, MTX, 
cyclosporine A, corticosteroids, 
cyclophosphamide)
N
N
Exception:  For patients with GPP 
or EP, methotrexate will be 
permitted before and during the 
study if doses are not greater than 
that of baseline, oral 
corticosteroids will be permitted 
before and during the study, if 
average daily doses are not greater 
than 10 mg/day of prednisone or its 
equivalent, and cyclosporine will 
be permitted until Week 2 (Visit 
4), if daily doses are not greater 
than that of baseline.  For these 
treatments, dose reductions are 
allowed but dose increases are not 
allowed during the study.

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Drug Class
Allowed for 
Chronic Use 
Allowed with 
Restrictions
Conditions for Allowed Use
*Systemic immunomodulating 
treatments (corticosteroids only)
N
Y
Limited use of systemtic 
corticosteroid ONLY as needed for 
limited, short-term medical 
management of TEAE may be 
considered.  Such drug class  might 
be considered psoriasis therapy if 
used under other regimens.  
Limited use during TEAE 
management is considered to not 
be consistent with psoriasis 
therapy.
Systemic psoriasis therapies 
(for example, retinoids, fumarates, 
apremilast)
N
N
Exception:  For patients with GPP 
or EP, oral retinoids will be 
permitted before and during the 
study if doses are not greater than 
that of baseline.  For this treatment, 
dose reductions are allowed but 
dose increases are not allowed 
during the study.
Bacillus Calmette-Guerin (BCG) 
vaccinations or live virus vaccinations 
(prohibited throughout the study and for 
12 months or 12 weeks, respectively, 
after discontinuation of study drug).
N
N
Any investigational treatment
N
N
Abbreviations:  EP = erythrodermic psoriasis; GPP = generalized pustular psoriasis; MTX = methotrexate; N = No; 
PUVA = psoralen and ultraviolet A; TEAE = treatment-emergent adverse event; UVA = ultraviolet A; UVB = 
ultraviolet B; Y = Yes.
4.6.
Section 8.2:  Discontinuation from the Study
In addition, patients who meet any one of the following criteria should be discontinued 
from the investigational product and enter the Post-Treatment Follow-Up Period, and 
discontinue from the study.

If a patient has a confirmed diagnosis of PCP during the study, the patient 
must discontinue the study (protocol Section 9.4.3.2 in Section 4.7 of this 
addendum). 
4.7.
Section 9:  Study Assessments and Procedures
9.1.4. Exploratory Efficacy Assessments for Patients at Sites in Japan
Assessment of Dermal Symptoms
Assessment of dermal symptoms, according to the Japanese Dermatological Association GPP 
revised criteria (Terui et al. [WWW]), will be performed only for patients with GPP.  Skin 
symptoms are assessed by the score with the area of erythema (on a 0-3 scale), erythema with 

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pustules (on a 0-3 scale), and area of skin edema (on a 0-3).  The total score will be assessed at 
visits indicated in the Schedule of Activities (Section 4.1 of this addendum).
Global Improvement Scores
Global improvement scores will be collected for patients with GPP or EP from Week 2.  Global 
improvement will be assessed in the 4 grades by comparing the psoriatic findings:  (1) resolved, 
(2) improved, (3) unchanged, (4) worsened.  The global improvement score is assessed based on 
the comparison of the psoriatic findings, sPGA, PASI score, and other evaluations with those at 
the baseline. The global improvement score will be assessed at visits indicated in the Schedule 
of Activities (Section 4.1 of this addendum).
9.2.1.  Serious Adverse Events
When an in-hospital patient enters the study (GPP, EP), the investigator should consider their 
past experience of treatment of psoriasis to evaluate whether mirikizumab prolonged the hospital 
stay of a patient.  Only if the investigator considers that mirikizumab truly prolonged the 
inpatient hospitalization, then worsening of the underlying condition of GPP or EP can be 
considered as an SAE.  
9.4.3.  Laboratory Tests
9.4.3.2  Laboratory Tests for Patients at Sites in Japan
Beta-D-glucan levels and KL-6 levels (biomarkers for PCP and interstitial lung disease, 
respectively) will be measured at screening and, if an investigator believes it is warranted, at 
subsequent visits. Either test may be included in the work up panel at any time during the study, 
including in the follow-up period.
If the beta-D-glucan test is positive, PCP needs to be ruled out.  If PCP is ruled out and the 
investigator deems the patient fit to continue, the patient may continue in the study.  If a patient 
has a confirmed diagnosis of PCP during the study, the patient must discontinue the study.
9.4.5.3.  Chest Radiography
Posterior-anterior (PA) chest x-ray (CXR) will be obtained at screening (Visit 1) unless, in the 
opinion of the investigator or based on local standard of care, both PA and lateral views are 
indicated.  In addition, chest radiography will be performed at Week 52, or for subjects who 
discontinue the study early if more than 12 weeks have elapsed since the previous study 
radiography was obtained.  If medically indicated, this radiography may be performed even 
when 12 weeks have not elapsed since the previous study radiography. Chest radiography may 
be performed at any time during the study, including the follow-up period, if medically necessary 
in the opinion of the investigator.
A CXR does not have to be performed if the patient has had a CXR that is sufficient for TB 
evaluation according to local standard of care within 3 months of screening, and the CXR film(s) 
or a radiology report is available to the investigator for review.
9.4.5.4.  Hepatitis B Screening

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Patients who test HBsAg+, test HBcAb+ in conjunction with positive confirmatory HBV DNA 
test, or have positive HBV DNA test, regardless of HBsAb status, at screening will be excluded.
Any enrolled subject who is HBcAb+ and/or HBsAb+ will undergo periodic monitoring of HBV 
DNA per the Schedule of Activities (Section 2).  
In addition to the above, any enrolled subject who is HBcAb+ and/or HBsAb+ and who 
experiences an elevated ALT or AST level >3× ULN must undergo HBV DNA testing.  If the 
HBV DNA test is negative, the investigator should consult with the Lilly-designated medical 
monitor regarding further management of the patient.
If the result of the HBV DNA test is positive but below quantification study drug should be 
withheld and a repeat test done immediately.  The Lilly-designated medical monitor should be 
contacted regarding study status of the patient.  If the result of the HBV DNA test is DNA 
positive and quantifiable, the patient must be discontinued from the study and should receive 
appropriate follow-up medical care, including consideration for antiviral therapy.  A specialist 
physician in the care of patients with hepatitis (for example, infectious disease or hepatologist 
subspecialists) should be consulted, and the patient should potentially be started on antiviral 
therapy prior to discontinuation of any immunosuppressant therapy (including study drug).  
Timing of discontinuation from the study treatment, the study, and of any immunosuppressant 
therapy (including study drug) needs to be based on the recommendations of the consulting 
specialist physician in conjunction with the investigator and medical guidelines/standard of care.  
4.8.
Section 10:  Statistical Considerations
10.1.  Sample Size Determination
In Cohort 1 (patients with plaque psoriasis), approximately 1443 patients will be randomized at a 
4:4:4:1 ratio in the Blinded Induction Period to receive 250 mg mirikizumab SC at Weeks 0, 4, 8, 
and 12, then 250 mg mirikizuamb SC Q8W, 250 mg mirikizumab SC at Weeks 0, 4, 8, and 12, 
then 125 mg mirikizumab SC Q8W, 300 mg secukinumab Q4W, or placebo.  Stratified block 
randomization will be performed with the following stratification factors:  previous exposure to 
biologic therapy (yes/no), body weight (<100 kg or 100 kg), and geographic region (North 
America, Europe or Other).
Eight patients with GPP and 8 patients with EP will be enrolled in Cohort 2 in Japan.  All 
patients in Cohort 2 will receive 250 mg mirikizumab SC at Weeks 0, 4, 8, and 12 during the 
Induction Period.  During the Maintenance Period, starting at Week 16, GPP and EP patients will 
receive 250 mg mirikizumab Q8W SC for up to a total of 52 weeks.  The number of patients with 
GPP and EP is based on the population size of these patients being very small in Japan 
(Umezawa et al. 2003, Rosenbach et al. 2010).
10.3.1. General Statistical Considerations
The benefit/risk profile to support global registrations will be based on the analysis of Cohort 1.
Patients enrolled in Cohort 2 will not be included in the analysis supporting global registrations.  
To support registration in Japan, efficacy and safety analysis for plaque psoriasis, GPP, and EP 

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will be conducted separately. Safety data for all patients (plaque psoriasis, GPP, EP) will also be 
assessed.
10.3.8. Interim Analyses
In addition, the sponsor may consider interim analyses of Cohort 2 for Japan regulatory 
communication purposes. In this case, collected data may be summarized. 

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5. References
[JSH] Drafting Committee for Hepatitis Management Guidelines and the Japan Society of 
Hepatology. JSH guidelines for the management of hepatitis B virus infection. Hepatol Res. 
2017(suppl S3):127-128.
Koike T, Harigai M, Inokuma S, Inoue N, Ishiguro N, Ryu J, Takeuchi T, Tanaka Y, 
Yamanaka H, Fujii K, Freundlich B, Suzukawa M. Postmarketing surveillance of safety and 
effectiveness of etanercept in Japan. J Rheumatol. 2009;36(5):898-906.
Ohtsuki M, Terui T, Ozawa A, Morita A, Sano S, Takahashi H, Komine M, Etoh T, Igarashi A, 
Torii H, Asahina A, Nemoto O, Nakagawa H; Biologics Review Committee of the Japanese 
Dermatological Association. Japanese guidance for use of biologics for psoriasis (the 2013 
version). J Dermatol. 2013;40(9):683-695.
Rosenbach M, Hsu S, Korman NJ, Lebwohl MG, Young M, Bebo BF Jr, Van Voorhees AS; 
National Psoriasis Foundation Medical Board. Treatment of erythrodermic psoriasis: from the 
medical board of the National Psoriasis Foundation. J Am Acad Dermatol. 2010;62(4):655-662.
Takeuchi T, Tatsuki Y, Nogami Y, Ishiguro N, Tanaka Y, Yamanaka H, Kamatani N, Harigai M, 
Ryu J, Inoue K, Kondo H, Inokuma S, Ochi T, Koike T. Postmarketing surveillance of the 
safety profile of infliximab in 5000 Japanese patients with rheumatoid arthritis. Ann Rheum 
Dis. 2008;67(2):189-194.
Takigawa M, Tomita Y, Hashimoto T, Iwatsuki K (eds). Standard Textbook of Dermatology. 9th 
ed. Tokyo: Igaku-Shoin; 2010:p106-109.
Tasaka S, Hasegawa N, Kobayashi S, Yamada W, Nishimura T, Takeuchi T, Ishizaka A. Serum 
indicators for the diagnosis of pneumocystis pneumonia. Chest. 2007;131(4):1173-1180.
Terui T, Akiyama M, Ikeda S, Ozawa A, Kanekura T, Kurosawa M, Komiyane M, Sano S, 
Nemoto O, Muto M, Yamanishi K, Iwatsuki K. Practice Guidelines 2014 for generalized 
pustular psoriasis (GPP). Available at:
https://www.dermatol.or.jp/uploads/uploads/files/guideline/nouhouseikansenguideline.pdf. 
Accessed January 16, 2017. 
Umezawa Y, Ozawa A, Kawasima T, Shimizu H, Terui T, Tagami H, Ikeda S, Ogawa H, 
Kawada A, Tezuka T, Igarashi A, Harada S. Therapeutic guidelines for the treatment of 
generalized pustular psoriasis (GPP) based on a proposed classification of disease severity. 
Arch Dermatol Res. 2003;295 Suppl 1:S43-S54.

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Attachment 1.Protocol Addendum AMAJ(1) Clinical 
Laboratory Tests
In addition to the clinical laboratory tests included on Appendix 2 of the protocol, the following laboratory tests 
are required under this addendum:
Clinical Chemistry
Serum Concentrations of:
Beta-D-glucan
KL-6
Other
HBV DNA testc
c
Following screening, patients will not undergo monitoring for Hepatitis C unless liver enzymes are elevated.  
Hepatitis B monitoring will be performed at protocol-specified intervals in patients who test positive for anti-
hepatitis B core antibody and/or positive for anti-hepatitis B surface antibody.

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Attachment 2.Protocol Addendum Revisions
Overview
Protocol Addendum I6T-MC-AMAJ(1) [A Multicenter, Randomized, Double-Blind, Placebo-
Controlled Study Comparing the Efficacy and Safety of Mirikizumab to Secukinumab and 
Placebo in Patients with Moderate-to-Severe Plaque Psoriasis] has been amended due to trial site 
requests regarding concomitant medication. The revised protocol addendum is indicated by 
revision (1.1) and will be used in place of any preceding version of this protocol addendum.
The overall change made to this protocol addendum is as follows:

Methotrexate or oral retinoids is permitted in addition to oral corticosteroids and 
cyclosporine

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Revised Protocol Addendum
Note:
Deletions have been identified by strikethroughs.
Addition to I6T-MC-AMAJ Clinical Protocol have been identified by the use of 
underscore.
Changes to I6T-MC-AMAJ (1.1) Clinical Protocol Addendum have been 
identified by the use of double underscore.
Section number was arranged.
[Before]
4.5.
Section 8.2:  Discontinuation from the Study
4.6.
Section 7.7:  Concomitant Therapy
[After]
4.5.
Section 7.7: Concomitant Therapy
4.6.
Section 8.2:  Discontinuation from the Study
4.2.
Section 4:  Objectives and Endpoints
Table AMAJ(1).1.
Objectives and Endpoints
To assess the efficacy of mirikizumab in patients 
with EP
EP ONLY
Time course of response to treatment as measured by the 
following measures:

global improvement score

change from baseline in PASI

change from baseline in DLQI total score
At Week 16 and Week 52:

global improvement score

change from baseline in PASI

change from baseline in DLQI total score
4.3.
Section 5:  Study Design
In parallel, the AMAJ(1) addendum will enroll Japanese patients who are diagnosed as GPP by 
the Japanese Dermatological Association or EP who have ≥1080% body surface area (BSA) 
involvement (with inflammatory erythema) (Cohort 2).  Approximately 8 patients with GPP and 
8 patients with EP will be enrolled in Cohort 2 in Japan.  
4.4.
Section 6:  Study Population

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6.2.  Exclusion Criteria
Have hepatitis B or test positive for hepatitis B virus (HBV) at screening, defined as: 
A. Positive for hepatitis B surface antigen (HBsAg+),
OR
B.
Positive for hepatitis B core antibody (HBcAb+) in conjunction with positive 
confirmatory HBV for HBV deoxyribonucleic acid (DNA) test,
OR
C.
Positive HBV DNA, regardless of anti-hepatitis B surface antibody (HBsAb) 
status.  Positive for hepatitis B surface antibody (HBsAb+) and positive 
confirmatory for HBV DNA
Note:  Patients who are HBcAb+ and/or HBsAb+ and HBV DNA negative 
may be enrolled in the study.  Patients who meet these criteria at screening 
will be monitored during the study as detailed in revised protocol 
Section 9.4.5.4 (Section 4.7 of this addendum).  
Prior/Concomitant Therapy
[24]
Have received systemic nonbiologic therapy (including, but not limited to, oral 
psoralen plus ultraviolet A [PUVA] light therapy; cyclosporine; corticosteroids; 
methotrexate; oral retinoids; apremilast; tofacitinib; mycophenolate mofetil; 
thioguanine; hydroxyurea; sirolimus; tacrolimus; azathioprine; leflunomide; 
fumaric acid derivatives; or 1, 25 dihydroxy vitamin D3 and analogues) or 
phototherapy (including either oral and topical PUVA light therapy, ultraviolet B, 
excimer laser, or self treatment with tanning beds or therapeutic sunbathing) 
within 28 days prior to baseline.
[24a] GPP/EP ONLY:

Methotrexate or oral retinoids will be permitted before and during the study if 
doses are not greater than that of baseline.

Oral corticosteroids will be permitted before and during the study, if average 
daily doses are not greater than 10 mg/day of prednisone or its equivalent.

Cyclosporine will be permitted until Week 2 (Visit 4), if daily doses are not 
greater than that of baseline or its equivalent.
4.5.
Section 7.7:  Concomitant Therapy
For patients with GPP or EP, methotrexate and oral retinoids will be permitted before and during 
the study if the patients have been using such medication before starting the study and if doses 
are not greater than that of baseline.  Ooral corticosteroids and all topical treatment will be 

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permitted before and during the study, if the patients have been using such medication before 
starting the study and if average daily doses are not greater than 10 mg/day of prednisone or its 
equivalent., and Ccyclosporine will be permitted until Week 2 (Visit 4), if the patients have been 
using such medication before starting the study and if daily doses are not greater than that of 
baseline or its equivalent.  For methotrexate, oral retinoids, oral corticosteroids and cyclosporine, 
dose reductions are allowed but dose increases of these drugs are not allowed during the study.  
All topical treatment will be permitted before and during the study.

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Table AMAJ(1).2.
Excluded Classes of Concomitant Medications or Classes with 
Restricted Use 
Drug Class
Allowed for 
Chronic Use 
Allowed with 
Restrictions
Conditions for Allowed Use
Topical treatment for psoriasis or any 
other skin condition 
(including but not limited to, 
corticosteroids, crisaborole, anthralin, 
calcipotriene, topical vitamin D 
derivatives, retinoids, tazarotene, 
pimecrolimus, tacrolimus, emollients 
and other nonprescription topical 
products containing urea, >3% salicylic 
acid, alpha- or beta-hydroxyl acids)
N
N
Exception:  For patients with GPP 
or EP, all topical treatments will be 
permitted.  These topical 
medications should not be used 
within approximately 12 hours 
prior to study visits.
Other systemic immunomodulating 
treatments (for example, MTX, 
cyclosporine A, corticosteroids, 
cyclophosphamide)
N
N
Exception:  For patients with GPP 
or EP, methotrexate will be 
permitted before and during the 
study if doses are not greater than 
that of baseline, oral 
corticosteroids will be permitted 
before and during the study, if 
average daily doses are not greater 
than 10 mg/day of prednisone or its 
equivalent, and cyclosporine will 
be permitted until Week 2 (Visit 
4), if daily doses are not greater 
than that of baseline.  For these 
treatments, dose reductions are 
allowed but dose increases are not 
allowed during the study.
*Systemic immunomodulating 
treatments (corticosteroids only)
N
Y
Limited use of systemtic 
corticosteroid ONLY as needed for 
limited, short-term medical 
management of TEAE may be 
considered.  Such drug class  might 
be considered psoriasis therapy if 
used under other regimens.  
Limited use during TEAE 
management is considered to not 
be consistent with psoriasis 
therapy.
Exception:  For patients with GPP 
or EP, oral corticosteroids 
permitted if average daily doses 
are not greater than 10 mg/day of 
prednisone or its equivalent.

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Drug Class
Allowed for 
Chronic Use 
Allowed with 
Restrictions
Conditions for Allowed Use
Systemic psoriasis therapies 
(for example, retinoids, fumarates, 
apremilast)
N
N
Exception:  For patients with GPP 
or EP, oral retinoids will be 
permitted before and during the 
study if doses are not greater than 
that of baseline.  For this treatment, 
dose reductions are allowed but 
dose increases are not allowed 
during the study.

Leo Document ID = 6222d326-ace9-457b-b374-ac10dd058be3
Approver: 
Approval Date & Time: 26-Apr-2018 20:56:10 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 26-Apr-2018 20:56:10 GMT
Signature meaning: Approved
PPD
PPD