Conditions: Psoriasis
Keywords: Interleukin-23 (IL-23)
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 1484
Healthy volunteers: no

Brief summary:
The reason for this study is to see how effective and safe mirikizumab is compared to secukinumab and placebo for moderate to severe plaque psoriasis.

Detailed description:

Arms:
arm 1: Participants received 250 Milligrams (mg) Mirikizumab once every four weeks (Q4W) by subcutaneous injection during blinded induction period followed by 250mg Mirikizumab once every eight weeks (Q8W) in maintenance period. Participants received matching placebo to blind Secukinumab. arm 2: Participants received 250mg Mirikizumab once every four weeks (Q4W) by subcutaneous injection during blinded induction period followed by 125mg Mirikizumab once every eight weeks (Q8W) in maintenance period. Participants received matching placebo to blind Secukinumab. arm 3: Participants received matching placebo at weeks 0, 1, 2, 3, 4, 8, and 12 by subcutaneous injection during blinded induction period followed by 250mg Mirikizumab Q4W from week 16 to 32 followed by 250mg Mirikizumab Q8W from week 32 to 48 in maintenance period. Participants received matching placebo to blind Secukinumab. arm 4: Participants received 300mg Secukinumab at weeks 0, 1, 2, 3, 4, 8, and 12 by subcutaneous injection during induction period followed by 300mg Secukinumab Q4W from week 16 to 52 in maintenance period. arm 5: Participants received 250mg Mirikizumab Q4W in induction period followed by 250mg Q8W in maintenance period by subcutaneous injection.

Interventions: intervention 1: Mirikizumab intervention 2: Placebo intervention 3: Secukinumab
Intervention descriptions: intervention 1: Administered SC intervention 2: Administered SC intervention 3: Administered SC

Protocol document:
Prot_002.pdf: 
 
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 
 
 


I6T-MC-AMAJ(1.1) Clinical Protocol Addendum
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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)


I6T-MC-AMAJ(1.1) Clinical Protocol Addendum
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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 


I6T-MC-AMAJ(1.1) Clinical Protocol Addendum
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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.


I6T-MC-AMAJ(1.1) Clinical Protocol Addendum
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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 


I6T-MC-AMAJ(1.1) Clinical Protocol Addendum
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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 


I6T-MC-AMAJ(1.1) Clinical Protocol Addendum
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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. 


I6T-MC-AMAJ(1.1) Clinical Protocol Addendum
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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.


I6T-MC-AMAJ(1.1) Clinical Protocol Addendum
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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 


I6T-MC-AMAJ(1.1) Clinical Protocol Addendum
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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.


I6T-MC-AMAJ(1.1) Clinical Protocol Addendum
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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

Prot_000.pdf: 
 
I6T-MC-AMAJ(b) Clinical Protocol 
 
 
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: 30-Sep-2019 
 
 


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Protocol I6T-MC-AMAJ(b)
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
EUDRA CTA: 2017-003286-10
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)
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Electronically Signed and Approved by Lilly:  01 March 2018.
Amendment (a) Electronically Signed and Approved by Lilly:  08 February 2019
Amendment (b) Electronically Signed and Approved by Lilly
on approval date provided below.
Approval Date: 30-Sep-2019 GMT


I6T-MC-AMAJ(b) Clinical Protocol
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Table of Contents
Section
Page
Protocol I6T-MC-AMAJ(b) 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
Table of Contents........................................................................................................................2
1.
Protocol Synopsis................................................................................................................9
2.
Schedule of Activities .......................................................................................................15
3.
Introduction ......................................................................................................................23
3.1.
Study Rationale............................................................................................................23
3.2.
Background..................................................................................................................23
3.3.
Benefit/Risk Assessment..............................................................................................24
4.
Objectives and Endpoints..................................................................................................26
5.
Study Design.....................................................................................................................29
5.1.
Overall Design .............................................................................................................29
5.1.1.
Screening Period..................................................................................................29
5.1.2.
Baseline and Double-Blinded Induction Period (Week 0 to 
Week 16) .............................................................................................................29
5.1.3.
Blinded Maintenance Period (Week 16 to Week 52 [36 
Weeks]) ...............................................................................................................29
5.1.4.
Post-Treatment Follow-Up Period (12 Weeks) .....................................................30
5.2.
Number of Participants.................................................................................................32
5.3.
End of Study Definition ...............................................................................................32
5.4.
Scientific Rationale for Study Design...........................................................................32
5.5.
Justification for Dose ...................................................................................................33
6.
Study Population...............................................................................................................35
6.1.
Inclusion Criteria..........................................................................................................35
6.2.
Exclusion Criteria ........................................................................................................38
6.3.
Rationale for Exclusion of Certain Study Candidates....................................................41
6.4.
Lifestyle Restrictions....................................................................................................41
6.5.
Screen Failures.............................................................................................................41
7.
Treatments........................................................................................................................42
7.1.
Treatments Administered .............................................................................................42
7.1.1.
Packaging and Labeling .......................................................................................43
7.2.
Method of Treatment Assignment ................................................................................43
7.2.1.
Selection and Timing of Doses.............................................................................43


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7.3.
Blinding .......................................................................................................................44
7.4.
Dosage Modification....................................................................................................44
7.5.
Preparation/Handling/Storage/Accountability...............................................................44
7.6.
Treatment Compliance .................................................................................................45
7.7.
Concomitant Therapy...................................................................................................45
7.8.
Treatment after the End of the Study............................................................................47
7.8.1.
Treatment after Study Completion........................................................................47
7.8.2.
Special Treatment Considerations ........................................................................47
7.8.2.1.
Management of Hypersensitivity Events, Including 
Injection Site Events.......................................................................................47
8.
Discontinuation Criteria ....................................................................................................49
8.1.
Discontinuation from Study Treatment.........................................................................49
8.1.1.
Permanent Discontinuation from Study Treatment ...............................................49
8.1.2.
Temporary Interruption (Withholding) of Study Treatment ..................................49
8.1.3.
Discontinuation of Inadvertently Enrolled Patients...............................................50
8.2.
Discontinuation from the Study....................................................................................50
8.3.
Lost to Follow-Up........................................................................................................52
9.
Study Assessments and Procedures ...................................................................................53
9.1.
Efficacy Assessments...................................................................................................53
9.1.1.
Primary Efficacy Assessments .............................................................................53
9.1.1.1.
Static Physician’s Global Assessment.............................................................53
9.1.1.2.
Psoriasis Area and Severity Index...................................................................53
9.1.2.
Secondary Efficacy Assessments..........................................................................53
9.1.2.1.
Static Physician’s Global Assessment.............................................................53
9.1.2.2.
Psoriasis Area and Severity Index...................................................................54
9.1.2.3.
Body Surface Area .........................................................................................54
9.1.2.4.
Nail Psoriasis Severity Index ..........................................................................54
9.1.2.5.
Psoriasis Scalp Severity Index ........................................................................54
9.1.2.6.
Palmoplantar Psoriasis Severity Index ............................................................54
9.1.2.7.
Health Outcomes Assessments........................................................................54
9.1.2.7.1.
Dermatology Life Quality Index ...............................................................54
9.1.2.7.2.
European Quality of Life–5 Dimensions-5 Levels-
Psoriasis ...................................................................................................55
9.1.2.7.3.
Work Productivity and Activity Impairment 
Questionnaire:  Psoriasis...........................................................................55
9.1.2.7.4.
Psoriasis Symptoms Scale.........................................................................55
9.1.2.7.5.
Medical Outcomes Study 36-Item Short-Form Health 
Survey ......................................................................................................56


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9.1.2.7.6.
16-Item Quick Inventory of Depressive 
Symptomatology Self-Report....................................................................56
9.1.2.7.7.
Treatment Satisfaction Questionnaire for Medication................................56
9.1.2.7.8.
Patient’s Global Assessment of Psoriasis ..................................................57
9.1.3.
Appropriateness of Assessments ..........................................................................57
9.2.
Adverse Events ............................................................................................................57
9.2.1.
Serious Adverse Events........................................................................................58
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions..........................................59
9.2.2.
Adverse Event Monitoring with a Systematic Questionnaire ................................59
9.2.3.
Adverse Events of Special Interest .......................................................................60
9.2.4.
Complaint Handling.............................................................................................61
9.3.
Treatment of Overdose.................................................................................................61
9.4.
Safety...........................................................................................................................61
9.4.1.
Electrocardiograms ..............................................................................................61
9.4.2.
Vital Signs ...........................................................................................................62
9.4.2.1.
Hypertension ..................................................................................................62
9.4.3.
Laboratory Tests ..................................................................................................62
9.4.3.1.
Pregnancy Testing ..........................................................................................62
9.4.4.
Immunogenicity Assessments ..............................................................................63
9.4.5.
Other Tests...........................................................................................................63
9.4.5.1.
Physical Examination .....................................................................................63
9.4.5.2.
Tuberculosis Screening...................................................................................64
9.4.5.3.
Chest Radiography .........................................................................................65
9.4.5.4.
Hepatitis B Screening .....................................................................................66
9.4.5.5.
Hepatitis C Screening .....................................................................................66
9.4.6.
Safety Monitoring ................................................................................................67
9.4.6.1.
Hepatic Safety Monitoring..............................................................................67
9.5.
Pharmacokinetics .........................................................................................................67
9.6.
Pharmacodynamics ......................................................................................................68
9.7.
Pharmacogenomics ......................................................................................................68
9.7.1.
Whole Blood Sample for Pharmacogenetic Research ...........................................68
9.8.
Biomarkers...................................................................................................................68
9.9.
Medical Resource Utilization and Health Economics ...................................................69
10.
Statistical Considerations ..................................................................................................70
10.1. Sample Size Determination ..........................................................................................70
10.2. Populations for Analyses..............................................................................................70
10.3. Statistical Analyses ......................................................................................................71
10.3.1.
General Statistical Considerations ........................................................................71


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10.3.1.1.
Missing Data Imputation ................................................................................72
10.3.1.2.
Multiple Comparisons/Multiplicity.................................................................72
10.3.2.
Treatment Group Comparability...........................................................................73
10.3.2.1.
Patient Disposition..........................................................................................73
10.3.2.2.
Patient Characteristics ....................................................................................73
10.3.2.3.
Concomitant Therapy .....................................................................................73
10.3.2.4.
Treatment Compliance....................................................................................73
10.3.3.
Efficacy Analyses ................................................................................................73
10.3.3.1.
Primary Analyses ...........................................................................................75
10.3.3.2.
Secondary Analyses........................................................................................75
10.3.3.3.
Exploratory Analyses .....................................................................................75
10.3.4.
Safety Analyses....................................................................................................76
10.3.5.
Pharmacokinetic/Pharmacodynamic Analyses......................................................76
10.3.6.
Evaluation of Immunogenicity .............................................................................77
10.3.7.
Other Analyses.....................................................................................................77
10.3.7.1.
Subgroup Analyses.........................................................................................77
10.3.7.2.
Psoriasis Symptoms Scale Psychometric Analysis ..........................................77
10.3.8.
Interim Analyses..................................................................................................78
11.
References ........................................................................................................................79
12.
Appendices .......................................................................................................................84


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List of Tables
Table
Page
Table AMAJ.1.
Schedule of Activities....................................................................................16
Table AMAJ.2.
Objectives and Endpoints...............................................................................26
Table AMAJ.3.
Treatment Regimens......................................................................................42
Table AMAJ.4.
Excluded Classes of Concomitant Medications or Classes with 
Restricted Use ...............................................................................................46
Table AMAJ.5.
Proposed Noninferiority Margin for Various Major Secondary and 
Other Secondary Endpoints with Noninferiority Tests in 
Study I6T-MC-AMAJ ...................................................................................75


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List of Figures
Figure
Page
Figure AMAJ.1. Illustration of study design for Clinical Protocol I6T-MC-AMAJ...................31


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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions........................................................................85
Appendix 2.
Clinical Laboratory Tests...............................................................................90
Appendix 3.
Study Governance Considerations..................................................................92
Appendix 4.
Examples of Infections That May Be Considered Opportunistic in the 
Setting of Biologic Therapy...........................................................................97
Appendix 5.
Risk Factors for Latent Tuberculosis Infection...............................................99
Appendix 6.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality..................101
Appendix 7.
Protocol Amendment I6T-MC-AMAJ(b) Summary:  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......................................................................................................102


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1. Protocol Synopsis
Title of Study:
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
Rationale: 
Mirikizumab (LY3074828) is a monoclonal, anti-interleukin-23 (anti-IL-23) antibody being 
developed for the treatment of immune-mediated diseases where the IL-23 pathway is thought to 
have a significant pathogenic role.  The neutralizing activity of mirikizumab binds to the p19 
subunit of the IL-23 molecule and does not bind IL-12.  Study I6T-MC-AMAJ (AMAJ) is a 
confirmatory study testing mirikizumab as a treatment for plaque psoriasis and is intended to 
support registration of this indication.  This Phase 3 trial is designed to evaluate the efficacy of 
mirikizumab versus secukinumab and placebo, as measured by improvement in disease severity 
and key patient-reported outcomes, and will contribute to the evaluation of the safety of 
mirikizumab.
Objective(s)/Endpoints:  
Objectives
Endpoints
Primarya,b
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to high levels of 
clinical response
At Week 16:

Proportion of patients with an sPGA (0,1) with 
at least a 2-point improvement from baseline

Proportion of patients achieving a 90% 
improvement in PASI from baseline (PASI 90)
Major Secondarya,b
To assess whether mirikizumab induction dosing 
is superior to placebo with respect to clinically 
meaningful response and highest levels of 
clinical response
At Week 16:

Proportion of patients achieving a 75% 
improvement in PASI (PASI 75)

Proportion of patients achieving a 100% 
improvement in PASI from baseline (PASI 100)
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to body surface area 
(BSA) affected by psoriasis
At Week 16:

Proportion of patients with ≤1% of BSA with 
psoriasis involvement


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To assess whether mirikizumab induction dosing is 
superior to placebo with respect to patient-reported 
outcomes
At Week 16:

Proportion of patients with a PSS symptoms 
score of 0 (free of itch, pain, stinging, and 
burning) in those with a PSS symptoms score 
1 at baseline

Proportion of patients achieving a DLQI total 
score of (0,1) with at least a 5-point 
improvement (reduction) from baseline in 
patients with a baseline DLQI total score 5
To assess whether mirikizumab induction dosing is 
noninferior to secukinumab with respect to high levels 
of clinical response
At Week 16:

Proportion of patients with an sPGA (0,1) with 
at least a 2-point improvement from baseline

Proportion of patients achieving PASI 90
To assess whether 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W maintenance dosing is 
noninferior to secukinumab with respect to high and 
highest levels of clinical response
At Week 52:

Proportion of patients achieving sPGA (0,1)

Proportion of patients achieving PASI 90

Proportion of patients achieving PASI 100
To assess whether 250 mg mirikizumab maintenance
Q8W and 125 mg mirikizumab Q8W dosing is 
superior to secukinumab with respect to high levels 
of clinical response
At Week 52:

Proportion of patients achieving sPGA (0,1)

Proportion of patients achieving PASI 90

Proportion of patients achieving PASI 100
Other Secondaryb
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to an early, clinically 
meaningful response
To compare mirikizumab to placebo with respect to 
clinical response and time to clinical response during 
the induction dosing period, and with respect to patient-
reported outcomes during the induction dosing period
At Week 4:

Proportion of patients achieving PASI 75
At Week 16 and various time points over the first 
16 weeks of dosing:

Proportion of patients achieving PASI 90

Change from baseline in PPASI total score in 
patients with palmoplantar involvement 
at baseline

Change in PSSI total score in patients with 
scalp involvement at baseline

Change from baseline in NAPSI total score in 
patients with fingernail involvement 
at baseline

Change from baseline on the SF-36 physical 
component summary (PCS) and mental 
component summary (MCS) 

Change from baseline on PatGA of disease 
severity

Change from baseline for the WPAI PSO 
scores (Absenteeism, Presenteeism, Work 
Productivity Loss, and Activity Impairment)


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
Change from baseline in QIDS-SR16 total 
score in those with a baseline QIDS-SR16 
total score 11

Proportion of patients achieving a DLQI total 
score of (0,1) with at least a 5-point 
improvement (reduction) from baseline in 
patients with a baseline DLQI total score 5

Proportion of patients achieving DLQI (0,1) 
with DLQI baseline score >1
To compare mirikizumab to secukinumab with respect 
to clinical response and time to clinical response during 
the induction dosing period, and with respect to patient-
reported outcomes during the induction dosing period
At Week 16 and various time points over the first 
16 weeks of dosing:

Proportion of patients achieving PASI 90 
To assess whether 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W maintenance dosing is 
noninferior to secukinumab with respect to high levels 
of clinical response
At Week 24:

Proportion of patients achieving PASI 90
At Week 52:

Proportion of patients achieving an sPGA (0)
To assess efficacy of 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W as compared to 
secukinumab with respect to clinical response
At Week 52 and at various time points during the 
Maintenance Dosing Period:

Proportion of patients achieving PASI 90

Proportion of patients achieving a DLQI total 
score of (0,1) with at least a 5-point 
improvement (reduction) from baseline in 
patients with a baseline DLQI total score 5

Proportion of patients achieving DLQI (0,1)
with DLQI baseline score >1
Evaluate the pharmacokinetics and 
pharmacokinetic/pharmacodynamic relationship of 
mirikizumab

Clearance and volume of distribution of 
mirikizumab

Relationship between mirikizumab exposure 
and efficacy (sPGA and PASI)
Abbreviations:  BSA = body surface area; DLQI = Dermatology Life Quality Index; MCS = mental component 
summary; NAPSI = Nail Psoriasis Severity Index;  PASI = Psoriasis Area and Severity Index; 
PASI 75/90/100 = 75%/90%/100% improvement in PASI from baseline; PatGA  = Patient’s Global 
Assessment; PCS = physical component summary ; PPASI = Palmoplantar Psoriasis Severity Index; 
PSS = Psoriasis Symptoms Scale; PSSI = Psoriasis Scalp Severity Index; Q8W = every 8 weeks; 
QIDS-SR16 = 16-item Quick Inventory of Depressive Symptomatology; SF-36 = Short Form 36-item Health 
Survey; sPGA = static Physician’s Global Assessment; WPAI PSO = Work Productivity Activity Impairment 
Questionnaire – Psoriasis.
a
All primary and major secondary endpoint analyses will utilize the multiplicity control technique called 
“graphical multiple testing procedure” to control the overall family-wise Type I error rate.
b
Note: A “clinically meaningful” response is a PASI 75 response, which represents at least a 75% decrease 
(improvement) from the baseline PASI score. A “high level” of clinical response is a PASI 90 response, which 
represents at least a 90% decrease (improvement) from baseline in PASI score, or sPGA (0,1) response, which 
represents an “almost clear” response.  The “highest level” of clinical response is a PASI 100 or sPGA (0) 
response, which represents complete resolution of psoriasis.


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Summary of Study Design:
Study AMAJ is a Phase 3, multicenter, randomized, double-blind, placebo- and active-
controlled, parallel-group, multi-period study.  The study design includes 2 treatment periods 
(Induction and Maintenance), which together last for up to 52 weeks, followed by a 12-week 
Post-Treatment Follow-Up period.  The study population consists of male or female patients 
aged 18 years or older at the time of screening who have chronic plaque psoriasis based on a 
confirmed diagnosis of chronic plaque psoriasis for at least 6 months, are candidates for 
phototherapy and/or systemic therapy, and have 10% body surface area (BSA) involvement, a 
static Physician’s Global Assessment (sPGA) score of 3, and a Psoriasis Area and Severity 
Index (PASI) score 12 at screening and at baseline.
Treatment Arms and Duration:
At Visit 2 (Week 0, baseline), patients who meet the study eligibility criteria will be randomly 
assigned to their induction and maintenance treatments with stratification based on previous 
exposure to biologic therapy (yes/no), body weight (<100 kg or 100 kg), and geographic region 
(North America, Europe, or Other). The treatment groups in the Blinded Induction Period are
250 mg mirikizumab or matching placebo (SC) administered at Weeks 0, 4, 8, and 12, and 
300 mg secukinumab administered at Weeks 0, 1, 2, 3, 4, 8, and 12.
Patients who were randomly assigned at baseline to receive mirikizumab in the Blinded 
Induction Period were also randomly assigned to receive either 250 mg mirikizumab every 
8 weeks (Q8W) subcutaneous (SC) or 125 mg mirikizumab Q8W SC in the Blinded 
Maintenance Period, with maintenance dosing starting at Week 16 and ending at Week 48.  
Patients who were randomized to placebo in the Blinded Induction Period will receive 250 mg 
mirikizumab SC every 4 weeks (Q4W) for Weeks 16 through 32 and 250 mg mirikizumab Q8W 
thereafter.  Patients who were randomized to 300 mg secukinumab SC in the Blinded Induction 
Period will continue this treatment with Q4W dosing in the Blinded Maintenance Period, starting 
at Week 16 and ending at Week 48.  Throughout the study, patients will receive placebo, as 
appropriate, to maintain the study blind across treatment groups.
The duration of treatment periods is 52 weeks.  The total duration of participation in this study
may be up to 68 weeks as detailed below.
Screening Period:  Up to 4 weeks.
Treatment Period:  Approximately 52 weeks.
Post-Treatment Follow-up Period:  Approximately 12 weeks after the last visit for patients 
who discontinue treatment prior to the Week 52 assessment or who are unable or not willing to 
participate in the long-term extension study (I6T-MC-AMAH).
Number of Patients:
Screened:  1872


I6T-MC-AMAJ(b) Clinical Protocol
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Randomized:  1443
Completed:  1152
Statistical Analysis:
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 mirikizumab 
SC Q8W, 250 mg mirikizumab SC at Weeks 0, 4, 8, and 12, then 125 mg mirikizumab SC Q8W, 
300 mg secukinumab at Weeks 0, 1, 2, 3, and 4, followed by 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).
With 888 patients in the mirikizumab group and 111 patients in the placebo group, the estimated 
power is at least 99% to test superiority of mirikizumab to placebo on PASI 90 at Week 16, and 
on sPGA (0,1) at Week 16, respectively, at alpha of 0.05 two-sided. With 888 patients in the 
mirikizumab group and 444 patients in the secukinumab group, the estimated power is at least 
90% to test noninferiority of mirikizumab to secukinumab at alpha of 0.025 one-sided with a 
noninferiority margin of 10% on PASI 90 at Week 16 and on sPGA (0,1) at Week 16. The 
assumed PASI 90 responses are 70% for the mirikizumab arm, 70% for the secukinumab arm, 
and 3% for the placebo arm.  The assumed sPGA 0 or 1 responses are 70% for the mirikizumab 
arm, 70% for the secukinumab arm, and 5% for the placebo arm. Both PASI 90 and sPGA (0,1) 
rates at Week 52 are estimated to be 75% for both mirikizumab dose groups, and 65% for 
secukinumab group.
In addition, with 444 patients in the 250 mg mirikizumab Q8W group, 444 patients in 125 mg 
mirikizumab Q8W group, and 444 patients in the secukinumab group, the study will have an 
estimated power of 90% to test superiority of 250 mg mirikizumab Q8W compared to 
secukinumab at alpha of 0.05 two-sided on PASI 90 at Week 52 and sPGA (0,1) at Week 52,
respectively, as well as 90% power to test superiority of 125 mg mirikizumab Q8W compared to 
secukinumab at alpha of 0.05 two-sided on PASI 90 at Week 52 and sPGA (0,1) at Week 52,
respectively. 
For assessments of the primary and major secondary endpoints and other categorical efficacy and 
health outcome endpoints, the Cochran–Mantel–Haenszel (CMH) test along with Non-
Responder Imputation (NRI) will be used to compare the treatment groups. The CMH 
stratification factors will be the same as those used in the stratified randomization scheme.  The 
CMH p-value will be provided.  In addition, the treatment difference in proportions will be 
provided along with the 95% 2-sided confidence interval estimate.
The prespecified graphical multiple testing approach (Bretz et al. 2011) will be implemented to 
control the overall Type I error rate at 2-sided alpha of 0.05, for superiority tests and at 1-sided 
alpha of 0.025 for non-inferiority tests, for the hypotheses for the primary and major secondary 
endpoints.  A Data Monitoring Committee (DMC) consisting of members external to Lilly will 


I6T-MC-AMAJ(b) Clinical Protocol
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be established for interim safety monitoring across all Phase 3 trials in patients with psoriasis.  A 
DMC charter will govern the role and responsibilities of DMC-related activities.


I6T-MC-AMAJ(b) Clinical Protocol
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2. Schedule of Activities


I6T-MC-AMAJ(b) Clinical Protocol
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Table AMAJ.1.
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
Informed Consent
X
Demographics
X
Height
X
Physical Examc
X
X
X
X
Weight
X
X
X
X
Inclusion/Exclusion 
Criteria  
X
X
Complete 
Medical/Surgical 
History & Habits
X
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Preexisting 
Conditions
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signs (BP, 
temperature, and 
pulse)d
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chest Radiography 
for TB Screening
Xe
PPD/QuantiFERON-
TB Gold/ T-
SPOT.TB® (per 
local guidelines)
Xf
ECG
X


I6T-MC-AMAJ(b) Clinical Protocol
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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
C-SSRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm Suppl 
Formh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm Follow-
up Formh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
QIDS-SR16 (patient 
completed)
X
X
X
X
X
IP Dosed
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Investigator 
Completed Clinical 
Efficacy Scales
PASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BSA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
sPGA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Facial Psoriasis
X
X
X
PSSIi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
NAPSIi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PPASIi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient Completed 
Health Outcomes 
Scalesj
PSS
|---------------------------Daily Electronic Diaryk------------------------|
X
X
X
DLQI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SF-36
X
X
X
PatGA
X
X
X
X
X
X
X
X
X
X
X
WPAI-PSO
X
X
X
X
X


I6T-MC-AMAJ(b) Clinical Protocol
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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
EQ-5D-5L-PSO
X
X
X
X
X
X
TSQM
X
X
X
X
X
Laboratory Tests
Hematologyl
X
X
X
X
X
X
X
X
X
X
X
X
X
Clinical Serum 
Chemistryl
X
X
X
X
X
X
X
X
X
X
X
X
X
Lipid Panel 
(fasting)m
X
X
X
Urinalysis
X
X
X
hsCRP
X
X
X
X
X
X
X
X
HBsAg, HBcAb, 
HBsAb
Xn
HBV DNA 
testingn
X
X
X
X
X
Hepatitis C 
Antibody
X
HCV RNA testing
X
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
HIV
X
Immunogenicity 
for mirip
X
X
X
X
X
X
X
X
X
X
Serum for miri 
Concentrations 
(PK)q
X
X
X
X
X
X
X
X
X
X
Serum Pregnancy 
Test (WCBP only)
X


I6T-MC-AMAJ(b) Clinical Protocol
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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
Urine Pregnancy 
Test (local; 
WCBP only)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
FSH
Xr
Serum/Plasma for 
Storage/Explorato
ry Biomarkers
X
X
X
X
Serum/Plasma for 
Storage/Explorato
ry IL-19 
Biomarker
X
X
X
X
X
X
X
X
X
X
X
X
Blood for RNA 
and DNA
Epigenetic 
Exploratory 
Biomarkers
X
X
X
X
Blood for DNA 
Pharmacogenetics
X


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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
Physical Examc
X
X
X
Weight
X
Concomitant Medications
X
X
X
Adverse Events
X
X
X
Vital Signs (BP, temperature, and pulse)d
X
X
X
ECG
Xg
Xg
C-SSRS
X
X
X
Self-Harm Suppl Formh
X
X
X
Self-Harm Follow-up Formh
X
X
X
QIDS-SR16
X
X
Investigator Completed Clinical Efficacy
Scales
PASI
X
X
X
BSA
X
X
X
sPGA
X
X
X
Facial Psoriasis
X
PSSIi
X
X
X
NAPSIi
X
X
X
PPASIi
X
X
X
Patient Completed Health Outcomes
Scalesj
PSS
X
DLQI
X
SF-36
X
PatGA
X
WPAI-PSO
X
EQ-5D 5L PSO
X
TSQM
X
Laboratory Tests
Hematologyl
X
X
Clinical Serum Chemistryl
X
X
Urinalysis
Xu
HBV DNA testingn
X
X
X
HCV RNA testing
Xo
Xo
Immunogenicity for mirip
X
X
Serum for miri Concentrations (PK)q
X
X
Urine Pregnancy Test (local; WCBP 
only)
X
X
X
Serum/Plasma for Storage/Exploratory 
Biomarkers
X
X


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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
Serum/Plasma for Storage/Exploratory 
IL-19 Biomarker
X
X
Blood for RNA and DNA Epigenetic 
Exploratory Biomarkers
X
X
Abbreviations:  BP = blood pressure; BSA = body surface area; C-SSRS = Columbia–Suicide Severity Rating Scale; 
DLQI = Dermatology Life Quality Index; DNA = deoxyribonucleic acid; ECG = electrocardiogram; 
EQ-5D-5L-PSO  = European Quality of Life–5 Dimensions–5 Levels–Psoriasis; ETV = early termination visit; 
FSH = follicle-stimulating hormone; HBcAb = anti-hepatitis B core antibody; HBsAb = hepatitis B surface 
antibody; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; ; hsCRP = high-sensitivity C-reactive protein; IL-19 = interleukin-19; IP = 
investigational product; LV = last study visit; miri = mirikizumab; NAPSI = Nail Psoriasis Severity Index; 
PASI = Psoriasis Area and Severity Index; PatGA = Patient’s Global Assessment; PK = pharmacokinetic; PPASI 
= Palmoplantar Psoriasis Severity Index; PPD = purified protein derivative; PSS = Psoriasis Symptoms Scale; 
PSSI = Psoriasis Scalp Severity Index; QIDS = 16-item Quick Inventory of Depressive Symptomatology; RNA = 
ribonucleic acid; SF-36 = Medical Outcomes Study 36-Item Short Form Health Survey; sPGA = static 
Physician’s Global Assessment; Suppl = supplement; TB = tuberculosis; TSQM = Treatment Satisfaction for 
Medication; V = visit; W = weeks; WCBP = women of childbearing potential; WPAI-PSO = Work Productivity 
Activity and Impairment Questionnaire – Psoriasis.
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).
c
One complete physical examination (excluding pelvic or rectal examinations), which includes heart, lungs, 
peripheral lymph nodes, and abdomen, and visual examination of all skin areas (including genitalia and breast 
areas) will be performed at screening.  All physical examinations throughout the study should include a 
symptom-directed evaluation as well as examination of heart, lungs, peripheral lymph nodes, and abdomen, and 
visual examination of all skin areas (including genitalia and breast areas).  See Section 9.4.5.1.
d
Sitting blood pressure, temperature, and pulse are to be obtained at approximately the same time as ECG 
measurements or blood sampling.  When multiple assessments are scheduled for the same visit, the preferred 
order of completion should be as follows:  ECG (if applicable), vital signs, and then blood sampling.  
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).  For 
additional details, see Section 9.4.5.3.
f
TB testing will be performed at screening unless it has been performed within 3 months before initial screening 
(provided the formal report is available for the investigator’s review).  It may also be performed after screening if 
clinically indicated.  TB testing will be performed locally using an interferon-release assay (IGRA; 
QuantiFERON®-TB Gold or T-SPOT.TB®) or a purified protein derivative (PPD) tuberculin skin test..  If PPD 
test is performed, patients will return 2 to 3 days afterwards to have their PPD test read.  For additional details on 
TB testing, see Exclusion Criterion [19] and Section 9.4.5.2.
g
The preferred order of completion is supine ECG prior to vital signs, blood sampling, or any other study 
procedures. For additional details on ECG collection, see Section 9.4.1. ECG should be performed at the ETV 
and Visit 802 only if there is early termination due to a cardiovascular event. 
h
A Self-Harm Follow-Up Form is to be completed only during visits for which there is at least 1 discrete self-
harm event identified on the Self-Harm Supplement Form (see Section 9.2.2).


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i
PSSI, NAPSI, and PPASI assessments applicable only if symptoms are present at baseline.
j
These assessments should be completed before administration of investigational product, before the patient’s
clinical examination, before the patient receives any tests or results, and before the patient’s health, health data, 
or emotions are discussed.
k
Electronic diaries will be distributed at the screening visit and collected at the Week 16 visit.
l
Unscheduled hematology or blood chemistry panels may be performed at the discretion of the investigator.
m Patients should not eat or drink anything except water for 12 hours prior to sample collection.
n
Any enrolled patient who is HBcAb+ will undergo monitoring of HBV DNA with HBV DNA testing (see 
Section 9.4.5.4). 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. 
o
Following screening, patients will not undergo monitoring for HCV RNA unless liver enzymes are elevated (see 
Section 9.4.5.5). Any patient with a positive HCV RNA test must be discontinued from the study and receive 
appropriate follow-up medical care, including consideration for antiviral therapy.
p
Immunogenicity samples should be collected prior to dosing on visits when mirikizumab is administered. A 
sample will be obtained at unscheduled visits if a patient develops an acute hypersensitivity event after 
administration of IP (see Section 7.8.2.1).
q
Scheduled PK samples are taken as an aliquot from the immunogenicity sample.  Unscheduled PK samples, 
obtained if a patient develops an acute hypersensitivity event after administration of IP (see Section 7.8.2.1), will 
be collected in a separate tube.
r
FSH test is to be performed at screening for women who have had spontaneous amenorrhea for 6 to 12 months to 
confirm lack of childbearing potential.
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 and V802.
u
Urinalysis assessed only for early termination due to an adverse event for which urinalysis is clinically indicated.


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3. Introduction
3.1.
Study Rationale
Mirikizumab (LY3074828) is a monoclonal, anti-interleukin-23 (anti-IL-23) antibody being 
developed for the treatment of immune-mediated diseases where the IL-23 pathway is thought to 
have a significant pathogenic role.  The neutralizing activity of mirikizumab binds to the p19 
subunit of the IL-23 molecule and does not bind IL-12. Study I6T-MC-AMAJ (AMAJ) is a 
confirmatory study testing mirikizumab as a treatment for plaque psoriasis and is intended to 
support registration of this indication.  This Phase 3 trial is designed to evaluate the efficacy of 
mirikizumab versus secukinumab and placebo, as measured by improvement in disease severity 
and key patient-reported outcomes. The data will contribute to the evaluation of the safety of 
mirikizumab.
3.2.
Background
The worldwide prevalence of psoriasis is nearly 3% (IFPA 2017), with rates varying across 
ethnic groups, ages, gender, and geographic regions (Parisi et al. 2013).  Histologically, psoriasis 
is characterized by inflammatory infiltrate and hyperproliferative keratinocytes, which retain 
intact nuclei (parakeratosis), elongation of rete ridges, and hyperconvoluted vasculature in the 
papillary dermis.  The infiltrate consists of prominent T cells, dendritic cells, and neutrophils in 
the dermis.  The dysregulation of the immune system, especially the activation of pathogenic T 
cells, has been well demonstrated to play an important role in psoriasis development.
A typical organ-specific, T-cell-driven inflammatory disease, psoriasis had been considered a 
T helper (Th) 1-type skin disease for decades, until a new Th population, Th17, was identified 
(Lew et al. 2004; Steinman 2007; Weaver et al. 2007).  Substantial clinical and basic research 
observations now suggest that the IL-23/Th17 axis is essential in the pathogenesis of psoriasis 
(Di Cesare et al. 2009).  IL-23, a member of the IL-12 family of cytokines, is a heterodimeric 
protein comprised of 2 subunits; the p40 subunit, which it shares with IL-12, and the p19 
subunit, believed to be specific to IL-23.  IL-23 is produced by antigen-presenting cells, such as 
dendritic cells and macrophages, and plays an important role in maintenance and amplification of 
Th17 cells (Lee et al. 2004; Piskin et al. 2004).  In addition, Th17 cells and their downstream 
effector molecules, including IL-17A, IL-17F, IL-21, IL-22, and tumor necrosis factor (TNF)-
alpha, are found at increased levels in human psoriatic skin lesions and circulation (Boniface et 
al. 2007; Lowes et al. 2008; Caruso et al. 2009; Kagami et al. 2010).
A number of IL-23 targeting molecules are being investigated for the treatment of immune-
mediated diseases.  The first biologic to demonstrate clinical benefit through IL-23 inhibition in 
such diseases was ustekinumab, which is a monoclonal antibody approved by the United States 
Food and Drug Administration (FDA) (Stelara® package insert 2017) and the European 
Medicines Agency (EMA) (Stelara Summary of Product Characteristics 2017) for the treatment 
of psoriasis, psoriatic arthritis, and Crohn’s disease and is being evaluated in a Phase 3 trial for 
the treatment of ulcerative colitis (NCT02407236).  Ustekinumab binds the p40 subunit common 
to IL-12 and IL-23; therefore, it targets both cytokines rather than IL-23 specifically.  Blockade 
of the IL-12 pathway may prevent Th1 cell–induced interferon blockade of Th17 cell 


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development, thus potentially limiting the clinical activity of p40 targeting antibodies.  
Experimental studies suggest that blocking the IL-23/Th17/IL-17 immune axis alone is sufficient 
to treat autoimmune inflammation (Monteleone et al. 2009).  One such therapy that specifically 
targets the p19 subunit of IL-23, guselkumab, has been approved for treatment of moderate-to-
severe plaque psoriasis by the United States FDA (TremfyaTM package insert 2017) and the 
EMA (Tremfya Summary of Product Characteristics 2017).  Other similar agents, including 
mirikizumab in Studies I6T-MC-AMAA (AMAA) and I6T-MC-AMAF (AMAF), have 
demonstrated clinical activity in plaque psoriasis (Krueger et al. 2015; Papp et al. 2015, 2017; 
Reich et al. 2017b).
3.3.
Benefit/Risk Assessment
Psoriasis remains an important public health challenge.  Therefore, there is a continuing need to 
develop treatment options with mechanisms of action that differ from existing therapies.  Clinical 
data with mirikizumab (Studies AMAA and AMAF), as well as clinical data with ustekinumab,
risankizumab, tildrakizumab, and guselkumab, support the hypothesis that IL-23 plays a 
significant role in the pathogenesis of psoriasis, and these compounds appear to have a favorable 
benefit/risk profile in patients with psoriasis.  
To assess the nonclinical toxicity of mirikizumab and establish a margin of safety (MOS) for 
clinical studies, 4-week and 6-month general toxicity studies in normal cynomolgus monkeys 
were conducted with evaluation of immunotoxicity, toxicokinetics, safety pharmacology (as part 
of the 4-week study), and fertility (as part of the 6-month study). The weekly administration of 
mirikizumab to cynomolgus monkeys resulted in no adverse mirikizumab-related findings at 
doses of 0 mg/kg (vehicle), 1 and 30 mg/kg (SC), or 100 mg/kg (intravenous [IV]) for 4 weeks, 
or at doses of 0, 10, and 100 mg/kg (SC) for 6 months.  Based on the lack of any toxicity at 
exposures exceeding the highest clinical exposure and lack of any tissue cross-reactivity, the 
nonclinical safety profile of mirikizumab supports clinical development of mirikizumab.  Plasma 
exposure in monkeys at the no-observed-adverse-effect-level (NOAEL) in the 4-week and 6-
month studies provided a 52- and 22-fold margin of safety, respectively, relative to the predicted 
human exposure at the highest proposed clinical dose and frequency of 250 mg administered SC 
every 4 weeks. 
After 16 weeks of treatment in Study AMAF, Psoriasis Area and Severity Index (PASI) 90 
responses in all mirikizumab treatment arms were significantly higher than placebo, with the 
highest responses in the 100-mg and 300-mg dosing groups. Overall frequencies of adverse 
events (AEs) were similar for mirikizumab- and placebo-treated patients (Reich et al. 2017b).
The doses and regimens planned for Study AMAJ were selected based on analyses of 
pharmacokinetic (PK), safety, and efficacy data from Phase 1 and Phase 2 studies, literature 
information for other anti-IL-23 antibodies, and nonclinical safety data.  In addition, blinded 
trial-level safety reviews will be conducted at periodic intervals throughout the study.  Interim 
safety analyses will be conducted by an external Data Monitoring Committee (DMC) to review 
unblinded safety data.  These monitoring and risk-mitigation actions, along with regular review 


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of AEs and laboratory data, will assist in the evaluation and management of potential risks 
associated with mirikizumab administration.
Given the published literature supporting positive clinical activity following blocking IL-23 in 
autoimmune/inflammatory diseases including psoriasis, the favorable safety and PK profile of 
mirikizumab, and the initial clinical activity observed for mirikizumab in subjects with psoriasis, 
the potential benefits of participating in Study AMAJ are expected to outweigh the potential 
risks.
More information about the known and expected benefits, risks, serious adverse events (SAEs) 
and reasonably anticipated AEs of mirikizumab are to be found in the Investigator’s Brochure 
(IB).


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4.
Objectives and Endpoints
Table AMAJ.2 shows the objectives and endpoints of the study.
Table AMAJ.2.
Objectives and Endpoints
Objectives
Endpoints
Primarya,b
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to high levels of 
clinical response
At Week 16:

Proportion of patients with an sPGA (0,1) with 
at least a 2-point improvement from baseline

Proportion of patients achieving a 90% 
improvement in PASI from baseline (PASI 90)
Major Secondarya,b
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to clinically 
meaningful response and highest levels of 
clinical response
At Week 16:

Proportion of patients achieving a 75% 
improvement in PASI (PASI 75)

Proportion of patients achieving a 100% 
improvement in PASI from baseline 
(PASI 100)
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to body surface area 
(BSA) affected by psoriasis
At Week 16:

Proportion of patients with ≤1% of BSA with 
psoriasis involvement
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to patient-reported 
outcomes
At Week 16:

Proportion of patients with a PSS symptoms
score of 0 (free of itch, pain, stinging, and 
burning) in those with a PSS symptoms score 
1 at baseline

Proportion of patients achieving a DLQI total 
score of (0,1) with at least a 5-point 
improvement (reduction) from baseline in 
patients with a baseline DLQI total score 5
To assess whether mirikizumab induction dosing is 
noninferior to secukinumab with respect to high levels 
of clinical response
At Week 16:

Proportion of patients with an sPGA (0,1) with 
at least a 2-point improvement from baseline

Proportion of patients achieving PASI 90
To assess whether 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W maintenance dosing is 
noninferior to secukinumab with respect to high and 
highest levels of clinical response
At Week 52:

Proportion of patients achieving sPGA (0,1)

Proportion of patients achieving PASI 90

Proportion of patients achieving PASI 100


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To assess whether 250 mg mirikizumab maintenance
Q8W and 125 mg mirikizumab Q8W dosing is
superior to secukinumab with respect to high levels 
of clinical response
At Week 52:

Proportion of patients achieving sPGA (0,1)

Proportion of patients achieving PASI 90

Proportion of patients achieving PASI 100
Other Secondaryb
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to an early, clinically 
meaningful response
To compare mirikizumab to placebo with respect to 
clinical response and time to clinical response during 
the induction dosing period, and with respect to 
patient-reported outcomes during the induction 
dosing period
At Week 4:

Proportion of patients achieving PASI 75
At Week 16 and various time points over the first 
16 weeks of dosing:

Proportion of patients achieving PASI 90

Change from baseline in PPASI total score in 
patients with palmoplantar involvement 
at baseline

Change in PSSI total score in patients with 
scalp involvement at baseline

Change from baseline in NAPSI total score in 
patients with fingernail involvement 
at baseline

Change from baseline on the SF-36 physical 
component summary (PCS) and mental 
component summary (MCS) 

Change from baseline on PatGA of disease 
severity

Change from baseline for the WPAI PSO 
scores (Absenteeism, Presenteeism, Work 
Productivity Loss, and Activity Impairment)

Change from baseline in QIDS-SR16 total 
score in those with a baseline QIDS-SR16 
total score 11

Proportion of patients achieving a DLQI total 
score of (0,1) with at least a 5-point 
improvement (reduction) from baseline in 
patients with a baseline DLQI total score 5

Proportion of patients achieving DLQI (0,1) 
with DLQI baseline score >1
To compare mirikizumab to secukinumab with respect 
to clinical response and time to clinical response during 
the induction dosing period, and with respect to 
patient-reported outcomes during the induction 
dosing period
At Week 16 and various time points over the first 
16 weeks of dosing:

Proportion of patients achieving PASI 90 
To assess whether 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W maintenance dosing is 
noninferior to secukinumab with respect to high levels 
of clinical response
At Week 24:

Proportion of patients achieving PASI 90
At Week 52:

Proportion of patients achieving an sPGA (0)


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To assess efficacy of 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W as compared to 
secukinumab with respect to clinical response
At Week 52 and at various time points during the 
Maintenance Dosing Period:

Proportion of patients achieving PASI 90

Proportion of patients achieving a DLQI total 
score of (0,1) with at least a 5- point 
improvement (reduction) from baseline in 
patients with a baseline DLQI total score 5

Proportion of patients achieving DLQI (0,1) 
with DLQI baseline score >1
Evaluate the pharmacokinetics and 
pharmacokinetic/pharmacodynamic relationship 
of mirikizumab

Clearance and volume of distribution of 
mirikizumab

Relationship between mirikizumab exposure 
and efficacy (sPGA and PASI)
Exploratory
To evaluate the potential development of anti-
mirikizumab antibodies and their potential relationship 
with efficacy, TEAEs, and mirikizumab exposure
At Week 16 and Week 52:

Relationship between TE-ADA and efficacy 
(sPGA and PASI)

Relationship between TE-ADA and TEAEs

Relationship between TE-ADA and 
mirikizumab pharmacokinetics
Abbreviations:  BSA = body surface area; DLQI = Dermatology Life Quality Index; MCS = mental component 
summary; NAPSI = Nail Psoriasis Severity Index;  PASI = Psoriasis Area and Severity Index; 
PASI 75/90/100 = 75%/90%/100% improvement in PASI from baseline; PatGA = patient’s global 
assessment; PCS = physical component summary ; PPASI = Palmoplantar Psoriasis Severity Index; 
PSS = Psoriasis Symptoms Scale; PSSI = Psoriasis Scalp Severity Index; Q8W = every 8 weeks; 
QIDS-SR16 = 16-item Quick Inventory of Depressive Symptomatology; SF-36 = Short Form 36-item Health 
Survey; sPGA = static Physician’s Global Assessment; TE-ADA = treatment-emergent anti-drug antibody;
TEAE = treatment emergent adverse event; WPAI PSO = Work Productivity Activity Impairment 
Questionnaire – Psoriasis.
a
All primary and major secondary endpoint analyses will utilize the multiplicity control technique called 
“graphical multiple testing procedure” to control the overall family-wise Type I error rate.
b
Note: A “clinically meaningful” response is a PASI 75 response, which represents at least a 75% decrease 
(improvement) from the baseline PASI score. A “high level” of clinical response is a PASI 90 response, which 
represents at least a 90% decrease (improvement) from baseline in PASI score, or sPGA (0,1) response, which 
represents an “almost clear” response.  The “highest level” of clinical response is a PASI 100 or sPGA (0) 
response, which represents complete resolution of psoriasis.


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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 
different mirikizumab doses and regimens, placebo, or secukinumab. The study is comprised of
2 treatment periods (Induction and Maintenance), which together last for up to 52 weeks, 
followed by a 12-week Post-Treatment Follow-Up period.
Study governance considerations are described in detail in Appendix 3.
5.1.1. Screening Period  
Patients will be evaluated for study eligibility ≤28 days before the baseline visit (Visit 2).  The 
patient will sign the informed consent form (ICF) prior to any study assessments, examinations, 
or procedures being performed.  Screening procedures will be performed according to the 
Schedule of Activities (Section 2).  Electronic diary collection will begin at screening, 
approximately ≤28 days prior to Visit 2 (baseline).  All inclusion and exclusion criteria are 
provided in Sections 6.1 and 6.2, respectively.
5.1.2. Baseline and Double-Blinded Induction Period (Week 0 to 
Week 16)
At Visit 2 (Week 0; baseline), patients who meet the study eligibility criteria will be randomly 
assigned to their induction and maintenance treatments with stratification based on previous 
exposure to biologic therapy (yes/no), body weight (<100 kg or 100 kg), and geographic region 
(North America, Europe, or Other).  The treatment groups in the Blinded Induction Period are
250 mg mirikizumab or matching placebo (SC) administered at Weeks 0, 4, 8, and 12, and 
300 mg secukinumab (SC) administered at Weeks 0, 1, 2, 3, 4, 8, and 12.  
Patients who discontinue the study for any reason during this period will stop treatment and 
continue to the early termination visit (ETV) and then complete the 12-week Post-Treatment 
Follow-up Period.
5.1.3. Blinded Maintenance Period (Week 16 to Week 52 [36 Weeks])
Patients who were randomly assigned at baseline to receive mirikizumab in the Blinded 
Induction Period were also randomly assigned to receive either 250 mg mirikizumab Q8W SC or 
125 mg mirikizumab Q8W SC in the Blinded Maintenance Period, with maintenance dosing 
starting at Week 16 and ending at Week 48.  Patients who were randomized to placebo in the 
Blinded Induction Period will receive 250 mg mirikizumab SC Q4W for Weeks 16 through 32 
and 250 mg mirikizumab Q8W thereafter.  Patients who were randomized to 300 mg 
secukinumab SC in the Blinded Induction Period will continue this treatment with Q4W dosing 
during the Blinded Maintenance Period, starting at Week 16 and ending at Week 48.


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Throughout the study, patients will receive placebo, as appropriate, to maintain the study blind 
across treatment groups.
A discontinuation criterion has been included for patients in any treatment group who remain at 
or above their baseline sPGA score at Week 16 (Visit 9) and Week 24 (Visit 11), or remain at or 
above their baseline PASI score at Week 16 (Visit 9) and Week 24 (Visit 11), to ensure patients 
who have not shown any benefit from study treatment are offered alternative therapies (see 
Section 8.2).
At Week 52, patients have one of the following options:
1. Enter Study I6T-MC-AMAH (AMAH), a long-term extension study in which patients 
receive 250 mg mirikizumab Q8W SC or 125 mg mirikizumab Q8W SC, 
OR
2. Discontinue study treatment and complete Study AMAJ’s 12-week Post-Treatment 
Follow-Up Period.
Patients who discontinue early from the study for any reason during this period will stop 
treatment and continue to the ETV and then the 12-week Post-Treatment Follow-up Period.
5.1.4. Post-Treatment Follow-Up Period (12 Weeks) 
Patients who do not enroll into Study AMAH or who discontinue early from Study AMAJ will 
complete the Post-Treatment Follow-Up Period (Visit 801 and Visit 802) of Study AMAJ.
For patients who have entered the Post-Treatment Follow-Up Period, psoriasis therapy with 
another agent(s), as determined appropriate by the investigator, is allowed.
Figure AMAJ.1 illustrates the study design.


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Abbreviations: LV = last study visit; miri = mirikizumab; Q4W = every 4 weeks; 
Q8W = every 8 weeks; SC = subcutaneous; 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 as shown (patients receiving 125 mg 
miri will receive 1 placebo injection at weeks they receive miri and 2 placebo injections 
at other times shown).  Dosing is via SC injection for all treatments in all periods.
Figure AMAJ.1.
Illustration of study design for Clinical Protocol I6T-MC-AMAJ.
Post-Treatment 
Follow-Up Period
W0
V2
W16
V9
W52
V18
LV+4w
V801
LV+12w
V802
Screening
Placebo W0, W1, 
W2, W3, W4, W8, 
W12
Primary Endpoint
250 mg miri W16, W24, 
W32, W40, W48 + 
Placebo W20, W28, 
W36, W44
125 mg miri W16, W24, 
W32, W40, W48 + 
Placebo W16, W20, 
W24, W28, W32, W36, 
W40, W44, W48
300 mg 
secukinumab
W0, W1, W2, W3, 
W4, W8, W12 
Induction
Period
Maintenance
Period
250 mg miri W0, W4, 
W8, W12 + Placebo 
W1, W2, and W3
W 4
V1
*
*
*
*
300 mg secukinumab Q4W
250 mg miri Q4W
at W16 to W32 
250 mg miri Q8W
at W40 and W48
+ Placebo W36, 
W44


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5.2.
Number of Participants
Approximately 1872 participants will be screened to achieve 1443 randomized participants for 
an estimated total of 888 participants randomized to mirikizumab, 444 randomized to 
secukinumab, and 111 randomized to placebo.
5.3.
End of Study Definition
End of the study is the date of the last visit or last scheduled procedure for the last patient.
5.4.
Scientific Rationale for Study Design
This study will examine the effect of mirikizumab versus placebo and versus an active 
comparator (secukinumab) in patients with moderate-to-severe plaque psoriasis.  Secukinumab 
was chosen as the active-comparator as it:

is a biologic inhibitor of IL-17, which has been shown to be a primary effector molecule 
in the pathogenesis of plaque psoriasis.  Currently, IL-17 inhibitors are the most effective 
biologic systemic therapies approved for the treatment of moderate-to-severe psoriasis.

has demonstrated effectiveness in the treatment of moderate-to-severe psoriasis and is 
approved for the treatment of adults with moderate-to-severe plaque psoriasis.

has an established safety profile
Thus, secukinumab has been selected as an appropriate active comparator for a direct 
comparison of efficacy of mirikizumab against a well-established biologic standard of care 
during a 52-week treatment period.
The 300-mg secukinumab dose administered at Weeks 0, 1, 2, 3, and 4, followed by 300 mg 
every 4 weeks is the approved dose regimen for adult patients with moderate-to-severe psoriasis 
(Cosentyx® Summary of Product Characteristics 2017; Cosentyx® [secukinumab] package insert 
2018).
During the Induction Dosing Period (Period 2), 250 mg mirikizumab will be compared to 300
mg secukinumab and placebo.  During the Maintenance Dosing Period (Period 3), 2 dose 
regimens, 250 mg and 125 mg, of mirikizumab will be compared to 300 mg secukinumab.  All 
treatment groups are detailed in Section 7.1, with the dose justification outlined in Section 5.5.
The study will not use a placebo-to-match for secukinumab. The study blind will be maintained 
as described in Section 7.3 using designated Unblinded Site Personnel to administer study
injections, and by using physical means of shielding the investigational product from the 
patients’ view as detailed in Section 7.1.
The Induction Dosing Period (Period 2) is designed to compare efficacy and safety of 
mirikizumab versus secukinumab and versus placebo in patients with psoriasis.  The selection of 
placebo as a comparator is justified on the basis that the most robust evaluation of efficacy can 
be made versus placebo treatment, to provide clear evidence on assay sensitivity, and to conclude 
non-inferiority of the test treatment to the active control by showing that the test treatment 
preserves a certain predetermined percentage of effect over placebo relative to the effect over 


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placebo demonstrated by the active control (FDA 2016).  The duration of the 16-week primary 
evaluation is sufficiently short that patients will receive placebo without lasting adverse effects.  
The efficacy of mirikizumab in treating psoriasis will be measured by the sPGA and PASI 
response scales, with the primary efficacy endpoint at Week 16.  These measures and the 16-
week endpoint are in alignment with efficacy endpoints for currently approved psoriasis 
therapies and with regulatory guidance (EMA 2004).  Steady-state exposure is expected to be 
reached within the 16-week time period (median half-life [t½] of mirikizumab is 10.5 days), and 
it is anticipated that a significant clinical effect will be observed within this timeframe based on 
previous studies with mirikizumab in patients with psoriasis.  
The Maintenance Dosing Period (Period 3) is designed to evaluate the maintenance of response
with 2 different dose regimens of mirikizumab (250 mg and 125 mg, Q8W) as compared to the 
comparator (300 mg secukinumab, Q4W), as well as assessment of safety data following at least 
1 year of treatment with mirikizumab.
The Post-Treatment Follow-Up Period (Period 4) is included for safety monitoring following the 
last study visit for patients who do not enroll in Study AMAH or discontinue early from Study 
AMAJ.
5.5.
Justification for Dose
The dose levels and regimens selected for this study were based primarily on analyses of interim 
PK, safety, and efficacy data from the Phase 2 Study AMAF, safety data from other clinical 
studies evaluating mirikizumab, and nonclinical safety data.
Safety Considerations
Single doses of up to 600 mg IV were evaluated in Study AMAA (healthy subjects and psoriasis 
patients) and up to 1200 mg IV in Study AMAD (healthy subjects); no dose-related safety or 
tolerability issues were observed in either study.  Evaluation of the safety data available to date 
in the ongoing Phase 2 studies in ulcerative colitis patients (Study I6T-MC-AMAC) and in 
Crohn’s disease patients (Study I6T-MC-AMAG) that are evaluating higher and more frequent 
dose regimens of up to 1000 mg IV Q4W for up to 52 weeks has not revealed any difference in 
the safety profile resulting from these higher exposures.
The margin of safety for the 250 mg Q4W SC induction dose regimen proposed for this study 
relative to the NOAEL level in the 6-month nonclinical toxicology study in cynomolgus 
monkeys is 22, based on area under the plasma concentration versus time curve.
No dose-related safety or tolerability issues have been observed in Study AMAF, including in 
patients who were non-responders and received a third dose of 300 mg SC at Week 16.  
Although the proposed 250 mg Q4W induction dose regimen for this study is expected to 
produce modestly higher average concentrations than the highest dose regimen evaluated in 
Study AMAF, the safety data collected in completed and ongoing clinical studies and from 
nonclinical toxicology studies supports the proposed dose regimens.


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Efficacy Considerations
In Study AMAF, doses of 30, 100, and 300 mg, administered Q8W SC, provided significant 
efficacy relative to placebo, with 100 and 300 mg achieving greater efficacy than 30 mg at 
Week 16.  The 300 mg dose provided the highest efficacy for the primary endpoint at Week 16 
(PASI 90) and demonstrated a trend towards providing higher PASI 90 and PASI 100 rates at 
earlier time points; the 300 mg dose also provided a more durable response following Week 16.  
Thus, results from Study AMAF indicate that the highest dose (300 mg) provided the greatest 
efficacy.
Results from Study AMAF also suggest that additional dosing, if given during the Induction 
Period, might have further improved efficacy at Week 16.  This suggestion is based on 
incremental benefits observed following a third dose administered to Week 16 nonresponders 
when assessed within 4 week to 8 weeks of that dose.  Model-based analyses and simulations 
indicate that 250 mg doses administered at Weeks 0, 4, 8, and 12 (1000 mg total) will maximize 
efficacy at the end of the 16-week Induction Period.  
A dosing regimen of 250 mg SC Q8W during the Maintenance Period is expected to maintain or 
further enhance the efficacy achieved at the end of the Induction Period.  The 250 mg dose is 
expected to achieve exposures and efficacy that are not distinguishable from that observed with 
300 mg dosing.  A second maintenance dosing regimen of 125 mg Q8W SC was chosen to 
determine whether efficacy could be maintained on a lower dosing regimen.  This second dosing 
regimen is expected to result in mirikizumab concentrations that have, in individual subjects, 
minimal overlap with the concentrations produced with the 250 mg mirikizumab Q8W SC 
regimen.
Formulation Considerations
A 125 mg/mL concentration was selected to provide the maximum amount of mirikizumab that 
could be delivered as a single subcutaneous injection (that is, 2 mL).  Therefore, a 2 mL dose of 
mirikizumab (delivered either as two 1-mL injections or a single 2-mL injection) would deliver 
250 mg of mirikizumab, which is comparable to the 300-mg dose that was evaluated in the Phase 
2 Study, AMAF.  The 125-mg dose will be delivered as a single 1-mL SC; this dose is 
comparable to the 100-mg dose evaluated in Study AMAF.
Therefore, based on all the available clinical and non-clinical data, the dose regimens planned for 
this study are expected to provide an acceptable safety profile while providing maximum clinical 
response in patients with plaque psoriasis.


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6.
Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
6.1.
Inclusion Criteria
Patients are eligible to be included in the study only if they meet all of the following criteria 
within the screening period, which is ≤28 days prior to the start of study treatment, unless 
otherwise specifically defined.
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
Patient Characteristics
[3a] Male patients:
No male contraception required except in compliance with specific local 
government study requirements.
[3b] Female patients:
Women not of child-bearing potential may participate and include those who are:
A. Infertile due to surgical sterilization (hysterectomy, 
bilateral oophorectomy, or tubal ligation), congenital 
anomaly such as mullerian agenesis; 
OR
B. Postmenopausal,  defined as:
i.
A woman at least 50 years of age with an intact 
uterus, not on hormone therapy, who has had either:
a.
Cessation of menses for at least 1 year,
OR


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b.
At least 6 months (or longer if required by 
local regulatory requirements) of spontaneous 
amenorrhea with a follicle-stimulating 
hormone >40 mIU/mL, 
OR
ii. A woman 55 years or older not on hormone therapy 
who has had at least 6 months of spontaneous 
amenorrhea,
OR
iii. A woman at least 55 years of age with a diagnosis of 
menopause prior to starting hormone replacement 
therapy.
Women of child-bearing potential:
A. Must test negative for pregnancy prior to initiation of 
treatment as indicated by a negative serum pregnancy test 
at the screening visit followed by a negative urine 
pregnancy test within 24 hours prior to exposure.
B. Must agree to either remain abstinent, if complete 
abstinence is their preferred and usual lifestyle, or remain 
in same-sex relationships, if part of their preferred and 
usual lifestyle, without sexual relationships with males.  
Periodic abstinence (for example, calendar, ovulation, 
symptothermal, post-ovulation methods), declaration of 
abstinence just for the duration of a trial, and withdrawal 
are not acceptable methods of contraception.
OR
Must use 2 effective methods of contraception for the 
entirety of the study. Abstinence or contraception must 
continue for 12 weeks following completion of 
investigational product administration.
i.
Two effective methods of contraception (such as male or female 
condoms with spermicide, diaphragms with spermicide or cervical 
sponges) will be used. The patient may choose to use a double-
barrier method of contraception. Barrier protection methods 
without concomitant use of a spermicide are not a reliable or 
acceptable method. Thus, each barrier method must include use of 
a spermicide. It should be noted that the use of male and female 
condoms as a double-barrier method is not considered acceptable 
due to the high failure rate when these methods are combined.


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ii. Of note, one of the two methods of contraception may be a highly 
effective (less than 1% failure rate) method of contraception (such 
as combination oral contraceptives, implanted contraceptives or 
intrauterine devices).
When local guidelines concerning highly effective or effective methods of birth 
control differ from the above, the local guidelines must be followed.
[4]
Are at least 18 years of age at the time of screening.
[5]
Have adequate organ function, including:
A. Hematology:
i.
Absolute neutrophil count 1.5 x 109/L (1.5 x 103/µL or 
1.5 GI/L),
ii.
Platelet count 100 x 109/L (100 x 103/µL or 100 GI/L), 
iii.
Hemoglobin level 10.0 g/dL (100 g/L), 
iv.
Lymphocyte count >500 cells/µL (>0.50 x 103/µL or >0.50 GI/L), 
v.
Total white blood cell count 3.0 x 109/L (3.0 x 103/µL or 
3.0 GI/L).
B. Chemistry:  
i.
Serum creatinine ≤2 times the upper limit of normal (ULN),
ii.
Alanine aminotransferase (ALT) ≤2 times ULN,
iii.
Aspartate aminotransferase (AST) levels ≤2 times ULN,
iv.
Total bilirubin level <1.5 times ULN (patients with Gilbert’s 
syndrome must have serum direct bilirubin <1.5 mg/dL or 
<25.7 µmol/L),
v.
Alkaline phosphatase (ALP) <1.5 times ULN.
(Note:  The tests for AST and ALT may be repeated once within a week 
if the initial response exceeds this limit, and the repeat value may be 
accepted if it meets this criterion.  Other laboratory tests should not be 
repeated unless there is a technical error or clinical reasons to believe a 
result may be erroneous, and requires approval by the Eli Lilly and 
Company [Lilly]-designated medical monitor.)
[6]
Are reliable and willing to make themselves available for the duration of the 
study, and are able and willing to follow study procedures, including use of 
electronic device for recording of data.


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Informed Consent
[7]
Have given written informed consent as a legal adult according to local 
regulations.
6.2.
Exclusion Criteria
Patients will be excluded from study enrollment if they meet any of the following criteria at 
screening unless otherwise specified:
Medical Conditions
[8]
Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the 
opinion of the investigator, increases the risks associated with participating in 
the study.
[9]
Have an unstable or uncontrolled illness, including but not limited to a 
cerebro-cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, 
hematologic, or neurologic disease or abnormal laboratory values at 
screening, that in the opinion of the investigator, would potentially affect 
patient safety within the study or of interfering with the interpretation of data.
[10] Presence of significant uncontrolled neuropsychiatric disorder or judged at
risk of suicide in the opinion of the investigator; 
OR 
marked “yes” to Columbia Suicidality Severity Rating Scale (C-SSRS)
question 4 or 5 on ideation at Visit 1, or prior to dosing at Visit 2;
OR 
“yes” to C-SSRS suicide behaviors question 1 month prior to Visit 1, or prior 
to dosing at Visit 2; 
OR 
Has a history of suicide attempt within 1 month prior to screening.
[11] Have human immunodeficiency virus (HIV)/acquired immune deficiency 
syndrome (AIDS) or test positive human HIV antibodies at screening.
[12] Have hepatitis C or test positive for hepatitis C virus (HCV) at screening, 
defined as:  positive result for hepatitis C antibody and positive confirmatory 
HCV ribonucleic acid (RNA) test (see Section 9.4.5.5).  Patients in sustained 
virologic response after HCV therapy, and patients who have spontaneously 
cleared HCV infection (see Section 9.4.5.5) , can be included in this study.
[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


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B.
Positive for hepatitis B core antibody (HBcAb+) in conjunction with positive 
confirmatory HBV deoxyribonucleic acid (DNA) test
OR
C.
Positive HBV DNA test, regardless of anti-hepatitis B surface antibody 
(HBsAb) status.
[14] Are women who are breastfeeding or plan to breastfeed during study.
[15] Have donated blood of >500 mL within 14 days prior to baseline.
[16] Have had serious, opportunistic (see Section 9.2.3 and Appendix 4), or 
chronic/recurring infection within 3 months prior to screening.  Examples 
include, but are not limited to, infections requiring IV antibiotics, 
hospitalization, or prolonged treatment.
[17] Have received a systemic (including oral) anti-infective agent for an infection 
within 28 days of baseline (see Section 6.5 for information on rescreening).
[18] Have had, according to the investigator, clinically significant herpes zoster 
within 3 months of screening.
[19] Have evidence of active or latent tuberculosis (TB) (refer to Section 9.4.5.2
for details on full TB exclusion criteria and Section 6.5 for information on 
rescreening).
[20] Have received a Bacillus Calmette-Guerin (BCG) vaccination within 
12 months or received live vaccine(s) (including attenuated live vaccines) 
within 12 weeks of baseline or intend to receive either during the study.
[21] Have history of hypersensitivity events to monoclonal antibodies or any 
components of the mirikizumab product formulation.
[22] Have active or history of lymphoma, leukemia, or any malignancy. 
Exceptions: the following conditions are not exclusionary:  successfully 
treated basal cell skin carcinoma, squamous cell skin carcinoma, or cervical 
carcinoma in situ, with no evidence of recurrence or metastatic disease within 
the 5 years prior to baseline.
[23] Have any other skin conditions (excluding plaque 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).


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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.
[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.
[26] Have prior use of secukinumab, or have any condition or contraindication as 
addressed in the local labeling for secukinumab that would preclude the 
patient from participating in this study.
[27] Have received anti-tumor necrosis factor (TNF) targeting biologics within 
8 weeks prior to baseline.
[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.
[29] Are unable or unwilling to avoid excessive sun exposure or use of tanning 
booths for at least 4 weeks prior to baseline and during the study.
Prior/Concurrent Clinical Trial Experience
[30] Are currently enrolled in any other clinical study involving an investigational 
product or any other type of medical research judged not to be scientifically or 
medically compatible with this study.
[31] Have participated, within the last 30 days in a clinical study involving an 
investigational product.  
If the previous investigational product has a long half-life, 3 months or 5 half-
lives (whichever is longer) should have passed prior to screening.
[32] Have previously completed or withdrawn from this study or any other study 
investigating mirikizumab.  


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Other Exclusions
[33] Are investigator site personnel directly affiliated with this study and/or their 
immediate families.  Immediate family is defined as a spouse, parent, child, or 
sibling, whether biological or legally adopted.
[34] Are Lilly employees or are employees of third-party organizations involved 
with the study that require exclusion of their employees.
[35] Are unsuitable for inclusion in the study in the opinion of the investigator or 
Sponsor for any reason that may compromise the patient’s safety or confound 
data interpretation.
6.3.
Rationale for Exclusion of Certain Study Candidates
Patients less than 18 years of age are excluded from participation in this study.  This is a 
confirmatory study designed to evaluate the efficacy and safety of mirikizumab as a treatment for 
plaque psoriasis and is intended to support registration of this indication in adult patients.  Until 
efficacy and an adequate safety profile is developed in adult patients with psoriasis, adolescents 
and younger children with psoriasis will not be included in studies of this investigational 
product.  Patients with particular medical conditions, including serious infections or other 
uncontrolled illnesses, are excluded for patient safety and to eliminate potential confounders to 
data interpretation.  Patients taking particular concomitant medications are excluded to eliminate 
potential confounders to data interpretation.  Exclusion of patients currently or recently enrolled 
in other clinical trials, or patients affiliated with the investigator or study Sponsor are excluded to 
meet Good Clinical Practice (GCP) initiatives for unbiased selection of patients.
6.4.
Lifestyle Restrictions
Study participants should be instructed not to donate blood or blood products during the study or
for 12 weeks following their last dose of investigational product.
6.5.
Screen Failures
Individuals may be rescreened only 1 time for failure due to criteria [17] or [19]. Patients who 
do not qualify at screening under Exclusion Criterion [17] (recent systemic anti-infective 
treatment) may be rescreened (1 time) 4 or more weeks after documented resolution of 
underlying condition being treated.  Patients who test positive for latent TB (Exclusion Criterion 
[19]) at screening may be rescreened following appropriate treatment as described in Section
9.4.5.2.
Each time rescreening is performed, the individual must sign a new ICF and will be assigned a 
new identification number.  
Patients who have had previous screening chest radiography and TB tests as per protocol within 
3 months of their rescreening date of consent do not need to repeat these procedures but may do 
so at the discretion of the investigator.


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7. Treatments
7.1.
Treatments Administered
This study involves a comparison of mirikizumab (250 mg or 125 mg) with secukinumab
(300 mg) or placebo administered SC during 52 weeks of double-blind treatment.  
Table AMAJ.3 shows the treatment regimens.
Table AMAJ.3.
Treatment Regimens
Regimen Group
Dosing
Description
250 mg miri Q4W
250 mg miri
(2 1-mL miri PFS)
At W0, 4, 8, and 12 for patients randomized to 
mirikizumab during the Induction Period.
At W16, 20, 24, 28, and 32 of the Maintenance 
Period, for patients who were randomized to 
placebo during the Induction Period.
250 mg miri Q8W
250 mg miri
(2 1-mL miri PFS)
During the Maintenance Period only, starting 
at W16.
125 mg miri Q8W
125 mg miri
(1 1-mL miri PFS plus 
1 x 1-mL placebo PFS)
During the Maintenance Period only, starting 
at W16.
300 mg secukinumab
300 mg secukinumab
(2 1-mL secukinumab PFS) W0, 1, 2, 3, 4, 8 and Q4W thereafter.
Placebo
Placebo
(2 x 1-mL placebo PFS)
At W0, 1, 2, 3, 4, 8, and 12 during the 
Induction Period.
Throughout the study, patients on miri and 
secukinumab treatments will receive placebo, 
as appropriate, to maintain the study blind 
across treatment groups.
Abbreviations:  miri = mirikizumab; PFS = prefilled syringe; Q4W = every 4 weeks; Q8W = every 8 weeks; 
W = week.
Detailed instructions for investigational product administration will be provided by the Sponsor, 
and the investigational product will be administered at the site by clinical staff. 
The investigator or his/her designee is responsible for the following:

Explaining the correct use of the investigational agent(s) to the site personnel,

Verifying that instructions are followed properly,

Maintaining accurate records of investigational product dispensing and collection,


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
At the end of the study returning all unused medication to Lilly, or its designee, 
unless the Sponsor and sites have agreed all unused medication is to be destroyed 
by the site, as allowed by local law.
Lilly will not provide a placebo to match secukinumab.  Therefore, in order to maintain the blind 
of this study, designated Unblinded Site Personnel will be responsible for dispensing of all 
investigational products (mirikizumab, secukinumab, and respective placebo). Unblinded Site 
Personnel will be responsible for administering the doses and maintaining the blind of the patient 
during the scheduled injections. This will be accomplished by physical means of shielding the 
investigational product from the patient’s view. Designated Unblinded Site Personnel will not be 
involved in any clinical aspects of the study, including clinical evaluations and AE 
assessments. During study drug preparation or administration, blinded persons will not be 
admitted to areas where study drug is being prepared or administered.  All study site personnel 
will be trained on the necessity to maintain the blind throughout the study.
7.1.1. Packaging and Labeling
Mirikizumab, placebo, and secukinumab will be supplied to the investigator by Lilly. Clinical 
trial materials will be labeled according to the country’s regulatory requirements. All 
investigational products will be stored, inventoried, reconciled, and returned or destroyed 
according to applicable regulations. Clinical trial materials are manufactured in accordance with 
current Good Manufacturing Practices (GMP).
Investigational product will be supplied as single-use, solution pre-filled syringes containing 
mirikizumab, secukinumab, or placebo.  The 1-mL syringe of mirikizumab is manufactured to 
contain 125 mg.  The 1-mL syringe of secukinumab is manufactured to contain 150 mg.
Mirikizumab cannot be distinguished visually from placebo.
Investigational product will be provided with study-specific labels. Syringes will be supplied in 
cartons, with the appropriate quantity specific to the planned dispensing schedule of the 
investigational product. 
7.2.
Method of Treatment Assignment
Patients who meet all criteria for enrollment will be randomized to double-blind treatment at 
Visit 2.  Assignment to treatment groups will be determined by a computer-generated random 
sequence using an interactive web-response system (IWRS).  The IWRS will be used to assign 
prefilled syringes containing double-blind investigational product to each patient.  
Investigational product will be dispensed according to the Schedule of Activities (Section 2) for 
treatment of patients in the clinic. Site personnel will confirm that they have located the correct 
carton(s) of pre-filled syringes by entering a confirmation number found on the carton(s) into the 
IWRS.
7.2.1. Selection and Timing of Doses
Study visits at which investigational product is administered are preferred, if possible, to occur 
on the same day of the week.  In any case, the study visits should occur within the visit window 


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specified on the Schedule of Activities (see Section 2).  The actual time of all dose 
administrations will be recorded in the subject’s electronic case report form (eCRF). 
7.3.
Blinding
This is a double-blind study.  The blinding applies to patients, site personnel, and Sponsor 
personnel.
To preserve the blinding of the study, a minimum number of Lilly and site personnel will see the 
randomization table and treatment assignments before the study is complete.
Emergency unblinding for AEs may be performed through the IWRS.  This option may be used 
ONLY if the patient’s well-being requires knowledge of the patient’s treatment assignment.  All 
actions resulting in an unblinding event are recorded and reported by the IWRS.
If an investigator, site personnel performing assessments, or patient is unblinded, the patient 
must be discontinued from the study.  In cases where there are ethical reasons to have the patient
remain in the study, the investigator must obtain specific approval from a Lilly-designated 
medical monitor for the patient to continue in the study.
In case of an emergency, the investigator has the sole responsibility for determining if unblinding 
of a patient’s treatment assignment is warranted for medical management of the event.  The 
patient safety must always be the first consideration in making such a determination.  If a 
patient’s treatment assignment is unblinded, Lilly must be notified immediately.  If the 
investigator decides that unblinding is warranted, it is the responsibility of the investigator to 
promptly document the decision and rationale and notify Lilly as soon as possible.
7.4.
Dosage Modification
Dose adjustments are not permitted in this study.
7.5.
Preparation/Handling/Storage/Accountability
The investigator or his/her designee is responsible for the following:

Confirming that appropriate temperature conditions have been maintained during 
transit for all study treatment received and any discrepancies are reported and 
resolved before use of the study treatment.

Ensuring that only participants enrolled in the study may receive study treatment 
and only authorized site staff may supply or administer study treatment. All study 
treatments must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions 
with access limited to authorized site staff.

The investigator, institution, or the head of the medical institution (where 
applicable) is responsible for study treatment accountability, reconciliation, and 
record maintenance (such as receipt, reconciliation and final disposition records).
Detailed instructions regarding supplies and preparation and handling of investigational products 
will be provided by the Sponsor.


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Investigational products will be supplied by Lilly or its representative, in accordance with current 
GMP and will be supplied with lot numbers, expiry dates, and certificates of analysis, as 
applicable. All investigational products will be stored, inventoried, reconciled, or destroyed 
according to applicable regulations.
Mirikizumab, placebo, and secukinumab should be transported and stored in refrigerated 
conditions 2°C to 8°C (36°F to 46°F).
7.6.
Treatment Compliance
All doses of study medication will be administered at the study site by site personnel.  Deviations 
from the prescribed dosage regimen should be recorded in the eCRF.
Every attempt will be made to select patients who have the ability to understand and comply with 
study instructions.  The investigator is responsible for discussing methods to ensure high 
treatment compliance with the patient before randomization.  
If a patient is noncompliant with study procedures and/or investigational product administration, 
the investigator should assess the patient to determine the reason for noncompliance and educate 
and/or manage the patient, as appropriate, to improve compliance.  Overall compliance with 
therapy is defined to be missing no more than 20% of the expected doses within the protocol-
defined visit window and not missing 2 consecutive doses.  If, in consultation with Lilly or its 
designee, the noncompliance is deemed to be significant or if further noncompliance occurs, the 
patient may be discontinued from the study.
7.7.
Concomitant Therapy
All concomitant medications taken during the study must be recorded on the Concomitant 
Medication 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.  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 is 
prohibited.  
Classes of therapies not permitted during the course of the study, or permitted with use 
restrictions, are specified in Table AMAJ.4 below (see also the Exclusion Criteria [Section 6.2]):


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Table AMAJ.4.
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
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, 
certolizumab)
N
N
Other systemic immunomodulating 
treatments (for example, MTX, 
cyclosporine A, corticosteroids,
cyclophosphamide)
N
N
.
Systemic immunomodulating treatments 
(corticosteroids only)
N
Y
Limited use of systemic
corticosteroids 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.


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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
Bacillus Calmette-Guerin (BCG) 
vaccinations or live virus vaccinations
(BCG prohibited for 12 months before 
baseline, live vaccinations prohibited for 
12 weeks before baseline.  Both are 
prohibited throughout the study and for 
12 week after discontinuation of study 
drug).
N
N
Any investigational treatment
N
N
Abbreviations:  MTX = methotrexate; N = No; PUVA = psoralen and ultraviolet A; TEAE = treatment-emergent 
adverse event; UVA = ultraviolet A; UVB = ultraviolet B; Y = Yes.
Topical therapies allowed during the study include shampoos that do not contain >3% salicylic 
acid, corticosteroids, coal tar, or vitamin D3 analogues; topical moisturizers/emollients and other 
non-prescription topical products that do not contain urea, >3% salicylic acid, alpha- or 
beta-hydroxyl acids, corticosteroids, or vitamin D3 analogues; and bath oils and oatmeal bath 
preparations. These topical therapies are not to be used within 12 hours prior to a study visit. 
For patients who have entered the Post-Treatment Follow-Up Period, psoriasis therapy with 
another agent(s), as determined appropriate by the investigator, is allowed.
7.8.
Treatment after the End of the Study
7.8.1. Treatment after Study Completion
Mirikizumab will not be made available to patients who either discontinue early from Study 
AMAJ or complete Study AMAJ but do not enroll in Study AMAH.
7.8.2. Special Treatment Considerations 
7.8.2.1.
Management of Hypersensitivity Events, Including Injection Site Events
All biological agents carry the risk of systemic allergic/hypersensitivity events.  Clinical 
manifestations of these events may include, but are not limited to:

Skin rash

Pruritus (itching) 

Urticaria (hives) 

Angioedema (for example, swelling of the lips and/or tongue) 

Anaphylactic events.
Sometimes, these events can be life-threatening.  Proteins may also cause redness, itching, 
swelling, or pain locally at the injection site.  Therefore, all patients should be closely monitored 


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for signs or symptoms that could result from such events, educated on the signs or symptoms of 
these types of events, and instructed to contact the study site immediately if any of the symptoms 
are experienced following an injection.  If a patient experiences an acute hypersensitivity event 
after an injection of investigational product, he or she should be managed appropriately and 
given instructions to receive relevant supportive care.
Additionally, for an event judged by the investigator to be a potential systemic hypersensitivity
event, blood samples will be collected for PK, immunogenicity, and exploratory hypersensitivity 
analyses at, or as close as possible to:
1. the onset of the event
2. the resolution of the event, and
3. 30 (±3) days following the event.
Exploratory hypersensitivity samples may, as appropriate for the clinical presentation,

be analyzed for tryptase (a marker of basophil/mast cell activation),

have a complement panel performed (asses immune complex formation), and

have a cytokine panel performed.
See also Section 9.4.4.
Patients who develop clinically significant systemic hypersensitivity events following 
administration of investigational product should be discontinued from the study and not receive 
further doses of investigational product, with or without premedication (see Section 8.2).


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8.
Discontinuation Criteria
8.1.
Discontinuation from Study Treatment
8.1.1. Permanent Discontinuation from Study Treatment
Patients for whom investigational product should be permanently discontinued, irrespective of 
the reason, should complete the Post-Treatment Follow-Up and then be permanently 
discontinued from the study. Section 8.2 provides the list of criteria for permanent 
discontinuation of patients from study treatment and the study.
Patients discontinuing from the investigational product prematurely for any reason should 
complete AE and other follow-up procedures per Section 2 (Schedule of Activities), Section 
5.1.4 (Post-Treatment Follow-up Period), Section 9.2 (Adverse Events), and Section 9.4 (Safety) 
of this protocol.
8.1.2. Temporary Interruption (Withholding) of Study Treatment
Some possible reasons for temporarily withholding investigational product include but are not 
limited to:

Development of:
o
Serious or opportunistic infections, as described in Section 9.2.3.
o
Hypertension (see Section 9.4.2.1),
o
Latent TB infection (LTBI) (see Section 9.4.5.2)
o
Positive HBV DNA results that are below the level of quantification (see 
Section 9.4.5.4).
o
Hepatic event or liver test abnormality:  Investigational product should be 
withheld and additional testing performed following consultation with the 
Lilly-designated medical monitor, if the results of repeat tests following elevated 
ALT, ALP or total bilirubin level (TBL) include one of the following 
(Section 9.4.6.1):

ALT 3x ULN and TBL <2x ULN

ALP 2x ULN and TBL <2x ULN

TBL 2x ULN without increase from baseline in ALT/AST/ALP.

Surgery:  Patients requiring surgery at any time during the study should interrupt 
administration of the investigational product, beginning 8 weeks before the surgery or as 
early as possible within 8 weeks of surgery, and resume administration of the 
investigational product only after complete wound healing.


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Cases that may merit temporary withholding of the study treatment will be discussed with the 
medical monitor.  The medical monitor, in consultation with the investigator, will determine 
when it is appropriate to recommence study treatment.
8.1.3. Discontinuation of Inadvertently Enrolled Patients
If the Sponsor or investigator identifies a patient who did not meet enrollment criteria and was 
inadvertently enrolled, then the patient should be discontinued from study treatment, unless there 
are extenuating circumstances that make it medically necessary for the patient to continue on 
study treatment.  If the investigator and the Sponsor-designated medical monitor agree it is 
medically appropriate to continue, the investigator must obtain documented approval from the 
Sponsor medical monitor to allow the inadvertently enrolled patient to continue in the study with 
or without treatment with the investigational product. Safety follow up is as outlined in Section
2 (Schedule of Activities), Section 9.2 (Adverse Events), and Section 9.4 (Safety) of the 
protocol.
8.2.
Discontinuation from the Study
Patients should permanently discontinue investigational product, complete the Post-Treatment 
Follow-up, and then permanently discontinue from the study for any of the following reasons:

Subject Decision
o
The patient requests to be either discontinued from the investigational product or 
withdrawn from the study.

Discontinuation due to a hepatic event or liver test abnormality.  Patients who are 
discontinued from investigational product due to a hepatic event or liver test abnormality 
should have additional hepatic safety data collected via eCRF.
Discontinuation of the investigational product for abnormal liver tests should be
considered by the investigator when a patient meets one of the following conditions after 
consultation with the Lilly-designated medical monitor:

ALT or AST >8x ULN

ALT or AST >5x ULN for more than 2 weeks

ALT or AST >3x ULN and TBL >2x ULN or international normalized 
ratio (INR) >1.5 

ALT or AST >3x ULN, with the appearance of fatigue, nausea, vomiting, 
right upper-quadrant pain or tenderness, fever, rash, and/or eosinophilia 
(>5%)

ALP >3x ULN

ALP >2.5x ULN and TBL >2x ULN

ALP >2.5x ULN, with the appearance of fatigue, nausea, vomiting, right 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)


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
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.

Total white blood cell (WBC) count <2000 cells/L (<2.00 x 103/µL or 
<2.00 GI/L).

Lymphocyte count <500 cells/μL (<0.50 x 103/µL or <0.50 GI/L).

Platelet count <50,000 cells/μL (<50 x 103/µL or <50 GI/L). 

Changes in blood pressure (BP) (systolic BP at 160 mm Hg plus 
20 mm Hg increase from baseline [Week 0; Visit 2]; and/or diastolic BP 
at 100 mm Hg plus 10 mm Hg increase from baseline) that do not 
respond following maximal allowed intervention (further explanation in 
Section 9.4.2).

The patient experiences a severe AE, an SAE, or a clinically significant 
change in a laboratory value occurs that, in the opinion of the investigator, 
merits the discontinuation of the investigational product.

Clinically significant systemic hypersensitivity event following 
administration of investigational product.

The patient becomes pregnant.

The patient develops a malignancy (Note: patients may be allowed to 
continue if they develop no more than 2 non-melanoma skin cancers 
during the study).

Any patient who has a change in disease phenotype at any time (for 
example, a change to pustular psoriasis).

If the patient remains at or above their baseline sPGA score at Week 16 
(Visit 9) and Week 24 (Visit 11), or remains at or above their baseline 
PASI score at Week 16 (Visit 9) and Week 24 (Visit 11).

It is recommended that the patient be assessed by an appropriately trained 
professional to assist in deciding whether the patient is to be discontinued 
from study treatment if:
i.
The patient, at any time during the study, scores a 3 for Item 12 
(Thoughts of Death or Suicide) on the 16-item Quick Inventory of 
Depressive Symptomatology (QIDS-SR16);
OR 
ii.
Develops active suicidal ideation with some intent to act with or 
without a specific plan (“yes” to question 4 or 5 on the “Suicidal 
Ideation” portion of the C-SSRS);
OR 
iii.
Develops suicide-related behaviors as recorded on the C-SSRS.


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
The patient develops active TB or HIV/AIDS during the study.

The patient becomes HBV (DNA) or HCV RNA positive.  The patient 
should be referred to a specialist physician (see Sections 8.1.2 and 9.4.5.4
for HBV, and Section 9.4.5.5 for HCV).

Patients will also be permanently discontinued from study drug, complete Post-
Treatment Follow-up, and then permanently discontinue from the study in the 
following circumstances:

Enrollment in any other clinical study involving an investigational product 
or enrollment in any other type of medical research judged not to be 
scientifically or medically compatible with this study

Participation in the study needs to be stopped for medical, safety, 
regulatory, or other reasons consistent with applicable laws, regulations, 
and GCP

Investigator decision

The investigator decides that the patient should be discontinued 
from the study

If the patient, for any reason, requires treatment with another 
therapeutic agent that has been demonstrated to be effective for 
treatment of the study indication, discontinuation from the study 
occurs prior to introduction of the new agent
Patients permanently discontinuing from investigational product, completing the Post-Treatment 
Follow-Up, and permanently discontinuing from the study prematurely for any reason should 
complete AE and other safety follow-up per Section 2 (Schedule of Activities), Section 5.1.4
(Post-Treatment Follow-up Period), Section 9.2 (Adverse Events), and Section 9.4 (Safety) of 
this protocol.
8.3.
Lost to Follow-Up
A patient will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site.  Site personnel are expected to make 
diligent attempts to contact patients who fail to return for a scheduled visit or were otherwise 
unable to be followed up by the site.


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9.
Study Assessments and Procedures
Section 2 lists the Schedule of Activities, with the study procedures and their timing (including 
tolerance limits for timing).
Appendix 2 lists the laboratory tests that will be performed for this study.
Unless otherwise stated in the subsections below, all samples collected for specified laboratory 
tests will be destroyed within 60 days of receipt of confirmed test results.  Certain samples may 
be retained for a longer period, if necessary, to comply with applicable laws, regulations, or 
laboratory certification standards.
9.1.
Efficacy Assessments
9.1.1. Primary Efficacy Assessments
The primary efficacy endpoints are the proportion of patients with an sPGA (0,1) with at least a 
2-point improvement from baseline at Week 16 and the proportion of patients achieving a 90% 
improvement in PASI from baseline (PASI 90) at Week 16.
9.1.1.1.
Static Physician’s Global Assessment
The sPGA is the physician’s global assessment of the patient’s psoriasis lesions at a given time 
point (EMA 2004).  Plaques are assessed for induration, erythema, and scaling, and an overall 
rating of psoriasis severity is given using the anchors of clear (0), minimal (1), mild (2), 
moderate (3), severe (4), or very severe (5).
9.1.1.2.
Psoriasis Area and Severity Index
The PASI is an accepted primary efficacy measurement for this phase of development of 
psoriasis treatments (EMA 2004).  The PASI combines assessments of the extent of body-surface 
involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, 
redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 
0 for no psoriasis to 72 for the most severe disease (Fredriksson and Pettersson 1978).  The PASI 
has been the most frequently used endpoint and measure of psoriasis severity in clinical trials 
(EMA 2004; Menter et al. 2008).  A clinically meaningful response is a PASI 75, which 
represents at least a 75% decrease (improvement) from the baseline PASI score.  Higher levels of 
clearance (PASI 90), as well as complete resolution of psoriasis (PASI 100), have become 
additional endpoints because of the increasing recognition of the association of higher clearance 
with greater health-related quality of life (HRQoL) (Puig 2015).
9.1.2. Secondary Efficacy Assessments
Secondary efficacy assessments will include the following:
9.1.2.1.
Static Physician’s Global Assessment
Both sPGA (0) and sPGA (0,1) will be assessed at various time points up to Week 52.  For 
assessment description, see Section 9.1.1.1.


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9.1.2.2.
Psoriasis Area and Severity Index
PASI 75, PASI 90, and PASI 100 will be assessed at various time points up to Week 52.  PASI 
75, 90, and 100 are the percentage improvements in PASI (75%, 90%, and 100%, respectively).  
For assessment description, see Section 9.1.1.2.
9.1.2.3.
Body Surface Area
Percent BSA will be evaluated as the percent involvement of psoriasis on each subject’s BSA on 
a continuous scale from 0% (no involvement) to 100% (full involvement), where 1% 
corresponds to the size of the patient’s hand (including the palm, fingers, and thumb) (National 
Psoriasis Foundation 2016).
9.1.2.4.
Nail Psoriasis Severity Index
The Nail Psoriasis Severity Index (NAPSI) is used to evaluate the severity of fingernail bed 
psoriasis and fingernail matrix psoriasis by area of involvement in the fingernail unit.  In this 
study, only fingernail involvement will be assessed.  The fingernail is divided with imaginary 
horizontal and longitudinal lines into quadrants.  Each fingernail is given a score for fingernail 
bed psoriasis (0 to 4) and fingernail matrix psoriasis (0 to 4) depending on the presence (score of 
1) or absence (score of 0) of any of the features of fingernail bed and fingernail matrix psoriasis
in each quadrant.  The NAPSI score of a fingernail is the sum of scores in fingernail bed and 
fingernail matrix from each quadrant (maximum of 8).  Each fingernail is evaluated, and the sum 
of all the fingernails is the total NAPSI score (range, 0 to 80). 
9.1.2.5.
Psoriasis Scalp Severity Index
The Psoriasis Scalp Severity Index (PSSI) measures the affected scalp area and the severity of 
clinical symptoms. The PSSI is a composite score derived from the sum of scores for erythema, 
induration, and desquamation multiplied by a score for the extent of scalp area involved (range, 0 
to 72). Higher scores indicate worse severity (Thaçi et al. 2015).
9.1.2.6.
Palmoplantar Psoriasis Severity Index
The Palmoplantar Psoriasis Severity Index (PPASI) is a composite score derived from the sum of 
scores for erythema, induration, and desquamation multiplied by a score for the extent of palm 
and sole area involvement (range, 0 to 72).
9.1.2.7.
Health Outcomes Assessments
The following patient-reported questionnaires will be administered according to the Schedule of 
Activities (Section 2) in countries where the questionnaires have been translated into the native 
language of the region and linguistically validated.  These assessments should be completed 
before administration of investigational product; before the patient’s clinical examination; before 
the patient receives any tests or results; and before the patient’s health, health data, or emotions 
are discussed.
9.1.2.7.1. Dermatology Life Quality Index
The Dermatology Life Quality Index (DLQI) is a validated, dermatology-specific, patient-
reported measure that evaluates a patient’s HRQoL.  This questionnaire has 10 items that are 
grouped in 6 domains, namely symptoms and feelings, daily activities, leisure, work and school, 
personal relationships, and treatment.  The recall period of this scale is over the “last week.”  


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Response categories include “not at all,” “a little,” “a lot,” and “very much,” with corresponding 
scores of 0, 1, 2, and 3, respectively, and unanswered (“not relevant”) responses scored as “0.”  
Totals range from 0 to 30 (less to more impairment) (Finlay and Khan 1994; Basra et al. 2008).  
A DLQI total score of 0 to 1 is considered as having no effect on a patient’s HRQoL, and a 5-
point change from baseline is considered as the minimal clinically important difference (MCID) 
threshold (Khilji et al. 2002; Hongbo et al. 2005).
9.1.2.7.2. European Quality of Life–5 Dimensions-5 Levels-Psoriasis 
The European Quality of Life–5 dimensions–5 levels (EQ–5D–5L) questionnaire is a widely 
used, generic questionnaire that assesses health status (EuroQol Group 1990; Herdman et al. 
2011).  The questionnaire consists of 2 parts.  The first part assesses 5 dimensions (mobility, 
self-care, usual activities, pain/discomfort and anxiety/depression) that have 5 possible levels of 
response (no problems, slight problems, moderate problems, severe problems, extreme problems.  
This part of the EQ–5D–5L can be used to generate a health state index.  The health state index 
score is calculated based on the responses to the 5 dimensions, providing a single value on a 
scale from less than 0 (where zero is a health state equivalent to death; negative values are 
valued as worse than dead) to 1 (perfect health), with higher scores indicating better health 
utility.  The second part of the questionnaire consists of a visual analog scale on which the 
patient rates their perceived health state from 0 (the worst health you can imagine) to 100 (the 
best health you can imagine).  The study will use the EQ–5D–5L–Psoriasis (EQ–5D–5L–PSO), 
which is a version of the EQ–5D–5L with two additional items related to psoriasis:  skin 
irritation and self-confidence (Swinburn et al. 2013).
9.1.2.7.3. Work Productivity and Activity Impairment Questionnaire:  Psoriasis
The Work Productivity and Activity Impairment-Psoriasis (WPAI-PSO) Questionnaire is a 
patient-reported instrument developed to measure the impact on work productivity and regular 
activities attributable to a specific health problem (psoriasis).  It contains 6 items that measure:  
1) employment status, 2) hours missed from work due to the psoriasis, 3) hours missed from 
work for other reasons, 4) hours actually worked, 5) degree of health affected-productivity while 
working, and 6) degree of health affected-productivity in regular unpaid activities.  Four scores 
are calculated from the responses to these 6 items:  absenteeism, presenteeism, work productivity 
loss, and activity impairment.  Scores are calculated as impairment percentages (Reilly et al. 
1993), with higher numbers indicating greater impairment and less productivity, that is, worse 
outcomes.
9.1.2.7.4. Psoriasis Symptoms Scale
The Psoriasis Symptoms Scale (PSS) is a patient-administered assessment of 4 symptoms (itch, 
pain, stinging, and burning); 3 signs (redness, scaling, and cracking); and 1 item on the 
discomfort related to symptoms/signs.  Respondents are asked to answer the questions based on 
their psoriasis symptoms.  
The overall severity for each individual symptom/sign from the patient’s psoriasis is indicated by 
selecting the number from a numeric rating scale (NRS) of 0 to 10 that best describes the worst 
level of each symptom/sign in the past 24 hours, where 0=no symptom/sign and 10=worst 
imaginable symptom/sign.


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The symptom severity scores, ranging from 0 to 10, are the values of the selected numbers 
indicated by the patient on the instrument’s horizontal scale.  Each of the 8 individual items will 
receive a score of 0 to 10 and will be reported as item scores for itch, pain, stinging, burning, 
redness, scaling, cracking, and discomfort.  In addition, a symptoms score ranging from 0 (no 
symptoms) to 40 (worst imaginable symptoms) and a signs score of 0 (no signs) to 30 (worst 
imaginable signs) will be reported.  
9.1.2.7.5. Medical Outcomes Study 36-Item Short-Form Health Survey
The Medical Outcomes Study 36-Item Short-Form Health Survey (SF 36) is a patient-reported, 
generic, HRQoL instrument originally published in 1992, with some item wordings and response 
options revised in 2000 (Ware and Sherbourne 1992; Ware 2000).  It consists of 36 questions 
measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical 
problems, role limitations due to emotional problems, general health perceptions, mental health, 
social function, and vitality.  The patient’s responses are solicited using Likert scales that vary in 
length, with 3–6 response options per item.  The SF-36 can be scored into the 8 health domains 
named above and two overall summary scores: physical component summary (PCS) and mental 
component summary (MCS) scores. The domain and summary scores range from 0 to 100; 
higher scores indicate better levels of function and/or better health.  The SF-36 version 2 (acute 
version) will be used, which utilizes the recall period of “the past week” (Ware 2000).
9.1.2.7.6. 16-Item Quick Inventory of Depressive Symptomatology Self-Report 
The QIDS-SR16 is a self-administered, 16-item instrument intended to assess the existence and 
severity of symptoms of depression as listed in the American Psychiatric Association’s 
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) (American 
Psychiatric Association 2013).  A patient is asked to consider each statement as it relates to the 
way they have felt for the past 7 days.  There is a 4-point scale for each item ranging from 0 to 3.  
The 16 items corresponding to 9 depression domains are summed to give a single score ranging 
from 0 to 27, with higher scores denoting greater symptom severity.  The domains assessed by 
the instrument include:  (1) sad mood, (2) concentration, (3) self-criticism, (4) suicidal ideation, 
(5) interest, (6) energy/fatigue, (7) sleep disturbance (initial, middle, and late insomnia or 
hypersomnia), (8) decrease/increase in appetite/weight, and (9) psychomotor 
agitation/retardation.
This instrument will also be used for AE monitoring (see Section 9.2.2).
9.1.2.7.7. Treatment Satisfaction Questionnaire for Medication
The Treatment Satisfaction Questionnaire for Medication (TSQM) is a self-administered 9 item 
measure to evaluate patient treatment satisfaction with medication in the domains of 
effectiveness (3 items), convenience (3 items), and global satisfaction (3 items). The recall 
period is the last 2-3 weeks or since the medication was last taken. Item formats include both a 
1-to-7-point or 1-to-5-point Likert scale. Higher scores indicate greater satisfaction (Bharmal et 
al. 2009).


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9.1.2.7.8. Patient’s Global Assessment of Psoriasis
The Patient’s Global Assessment of Psoriasis (PatGA) is a patient-reported, single-item scale on 
which patients are asked to rank, by selecting a number on a 0 to 5 NRS, the severity of their 
psoriasis “today,” from 0 (clear/ no psoriasis) to 5 (severe).
9.1.3. Appropriateness of Assessments
The clinical safety parameters in this study are standard elements of clinical health assessment 
and Phase 3 drug development.  The disease activity and health outcome measurements are used 
both in clinical practice and psoriasis clinical trials.  Psoriasis is associated with numerous skin-
based symptoms and HRQoL impairment, which justifies the use of the psoriasis symptom 
severity as well as dermatologic and generic HRQoL assessments used in this study (EMA 2004; 
Kimball et al. 2005).
9.2.
Adverse Events
Investigators are responsible for monitoring the safety of patients who have entered this study 
and for alerting Lilly or its designee to any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the patient.
The investigator is responsible for the appropriate medical care of patients during the study.
Investigators must document their review of each laboratory safety report.
The investigator remains responsible for following, through an appropriate health care option, 
AEs that are serious or otherwise medically important, considered related to the investigational 
product or the study, or that caused them to discontinue the investigational product before 
completing the study.  The patient should be followed until the event resolves, stabilizes with 
appropriate diagnostic evaluation, or is reasonably explained.  The frequency of follow-up 
evaluations of the AE is left to the discretion of the investigator.
Lack of drug effect is not an AE in clinical studies, because the purpose of the clinical study is to 
establish treatment effect.
After the ICF is signed, study site personnel will record via eCRF the occurrence and nature of 
each patient’s preexisting conditions, including clinically significant signs and symptoms of the 
disease under treatment in the study.  In addition, site personnel will record any change in the 
condition(s) and any new conditions as AEs. Investigators should record their assessment of the 
potential relatedness of each AE to protocol procedure or investigational product via eCRF.
The investigator will interpret and document whether or not an AE has a reasonable possibility 
of being related to study treatment, study device, or a study procedure, taking into account the
disease, concomitant treatment or pathologies.
A “reasonable possibility” means that there is a cause and effect relationship between the 
investigational product, study device, and/or study procedure and the AE.
The investigator answers yes/no when making this assessment.


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Planned surgeries and nonsurgical interventions should not be reported as AEs unless the 
underlying medical condition has worsened during the course of the study.
If a patient’s investigational product is discontinued as a result of an AE, study site personnel 
must report this to Lilly or its designee via eCRF clarifying if possible, the circumstances leading 
to any dosage modifications, or discontinuations of treatment.
9.2.1. Serious Adverse Events
An SAE is any AE from this study that results in one of the following outcomes:

Death

Initial or prolonged inpatient hospitalization

A life-threatening experience (that is, immediate risk of dying)

Persistent or significant disability/incapacity

Congenital anomaly/birth defect

Important medical events that may not be immediately life-threatening or result in 
death or hospitalization, but may jeopardize the patient or may require 
intervention to prevent one of the other outcomes listed in the definition above.  
Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse.

When a condition related to the prefilled syringes necessitates medical or surgical 
intervention to preclude either permanent impairment of a body function or 
permanent damage to a body structure, the serious outcome of “required 
intervention” will be assigned.
All AEs occurring after signing the ICF are recorded in the eCRF and assessed for serious 
criteria.  The SAE reporting to the Sponsor begins after the patient has signed the ICF and has 
received investigational product.  However, if an SAE occurs after signing the ICF, but prior to 
receiving investigational product, the SAE should be reported to the Sponsor as per SAE 
reporting requirements and timelines (see Section 9.2) if it is considered reasonably possibly 
related to study procedure.
Study site personnel must alert Lilly or its designee of any SAE within 24 hours of investigator 
awareness of the event via a Sponsor-approved method.  If alerts are issued via telephone, they 
are to be immediately followed with official notification on study-specific SAE forms.  This 24-
hour notification requirement refers to the initial SAE information and all follow-up SAE 
information. Patients with a serious hepatic AE should have additional data collected using the 
eCRF.
Pregnancy (during maternal or paternal exposure to investigational product) does not meet the 
definition of an AE.  However, to fulfill regulatory requirements any pregnancy should be 
reported following the SAE process to collect data on the outcome for both mother and fetus.


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Investigators are not obligated to actively seek AEs or SAEs in patients once they have 
discontinued and/or completed the study (the patient disposition CRF has been completed).  
However, if the investigator learns of any SAE, including a death, at any time after a patient has 
been discharged from the study, and he/she considers the event reasonably possibly related to the 
study treatment or study participation, the investigator must promptly notify Lilly.
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the investigator identifies as related to investigational product or procedure.  
United States 21 CFR 312.32 and European Union Clinical Trial Directive 2001/20/EC and the 
associated detailed guidances or national regulatory requirements in participating countries 
require the reporting of SUSARs. Lilly has procedures that will be followed for the 
identification, recording and expedited reporting of SUSARs that are consistent with global 
regulations and the associated detailed guidances.
9.2.2. Adverse Event Monitoring with a Systematic Questionnaire 
The C-SSRS captures the occurrence, severity, and frequency of suicidal ideation and/or
behavior during the assessment period.  The scale includes suggested questions to solicit the type 
of information needed to determine if suicidal ideation and/or behavior occurred.  The C-SSRS is
administered by an appropriately trained health care professional with at least 1 year of patient 
care/clinical experience.  The tool was developed by the National Institute of Mental Health trial 
group for the purpose of being a counterpart to the Columbia Classification Algorithm of Suicide 
Assessment categorization of suicidal events.  For this study, the scale has been adapted (with 
permission from the scale authors) to include only the portion of the scale that captures the 
occurrence of the 11 preferred ideation and behavior categories.
The nonleading AE collection should occur prior to the collection of the C-SSRS.  If a 
suicide-related event is discovered during the C-SSRS but was not captured during the 
nonleading AE collection, sites should not change the AE form.  If an event is serious or leads to 
discontinuation, this is an exception where the SAE and/or AE leading to discontinuation should 
be included on the AE form and the process for reporting SAEs should be followed.
Suicide-related events (behavior and/or ideations) will be assessed and evaluated at every visit 
with the administration of the C-SSRS and the Self-Harm Supplement Form.  The Self-Harm 
Supplement Form is a single question to enter the number of suicidal behavior events, possible 
suicide behaviors, or nonsuicidal self-injurious behaviors.  If the number of behavioral events is 
greater than zero, it will lead to the completion of the Self-Harm Follow-Up Form.  The 
Self-Harm Follow-Up form is a series of questions that provides a more detailed description of 
the behavior cases.
The QIDS-SR16 instrument (for description, see Section 9.1.2.7.6) will be used to collect 
patient-reported data on signs and symptoms related to depression.


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9.2.3. Adverse Events of Special Interest
Adverse events of special interest (AESIs) are AEs which the Sponsor specifies as being of 
special interest based on standard drug registration topics, safety findings from previous studies 
in development program, potential risks associated with biologic immunomodulators as noted in 
product labels and published literature, and comorbidities and risk factors prevalent in the 
studied populations.  The AESIs for this study are defined in the statistical analysis plan (SAP), 
and may include, but not be limited to the following:

Infections, including opportunistic infections

Hypersensitivity events, including anaphylaxis

Injection site events

Cerebro-cardiovascular events

Malignancies

Depression or suicidal ideation or behaviors

Hepatic AEs.
For some AESIs, sites should provide additional information regarding the event, as instructed 
on the eCRF.
Infections, Including Opportunistic Infections
Drugs that modulate the immune system may increase the risk of infection, including serious or 
opportunistic infections.
Infections will be categorized by Lilly as opportunistic according to Opportunistic Infections and 
Biologic Therapies in Immune-Mediated Inflammatory Diseases: Consensus Recommendations 
for Infection Reporting during Clinical Trials and Postmarketing Surveillance by Winthrop et al. 
(2015).  Examples are listed in Appendix 4.
Hypersensitivity Events 
Site personnel should educate patients and/or caregivers about the symptoms and signs of 
hypersensitivity events and provide instructions on dealing with these events.  A blood sample 
will be collected when possible for any patient who experiences an AE of hypersensitivity during 
the study.
Cerebro-Cardiovascular Adjudication
Data collected regarding a potential or actual cerebro-cardiovascular AE will be provided to, and 
adjudicated by, an independent, external adjudication committee.  The role of the committee is to 
adjudicate the reported cardiovascular AEs in a blinded, consistent, and unbiased manner 
throughout the course of the study, thereby ensuring that all such reported events are evaluated 
uniformly.


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9.2.4. Complaint Handling
Lilly collects product complaints on investigational products and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and to 
facilitate process and product improvements.
Patients will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product or prefilled syringes so that the situation 
can be assessed.
•
Complaints must be reported by site staff within 24 hours of study/site personnel becoming 
aware of a product issue, regardless of the availability of the complaint sample.  
•
Investigational product should be retained under appropriate storage conditions, if available 
or when obtained, until instructed to return it to Lilly or its designee.  
•
Product complaints for non-Lilly products (including concomitant drugs) that do not have a 
Lilly Product Batch or Control number are reported directly to the manufacturer per product 
label.
•
Instructions outlined in the Product Complaint Form should be followed for other reporting 
requirements.
9.3.
Treatment of Overdose
Investigators should remain vigilant for unknown effects related to mirikizumab overdose.  In 
case of suspected overdose, hematology, chemistry, vital signs, and oxygen saturation should be 
monitored and supportive care provided as necessary.  There is no known antidote for 
mirikizumab.  
Refer to the Product Label of secukinumab for advice on overdose.
9.4.
Safety
9.4.1. Electrocardiograms
For each patient, ECGs should be collected according to the Schedule of Activities (Section 2).  
Electrocardiograms should be recorded according to the study-specific recommendations and 
read locally for evaluation of study eligibility and safety monitoring.
Patients should be supine for approximately 5 to 10 minutes before ECG collection and remain 
supine but awake during ECG collection.  Sitting BP, temperature, and pulse (see Section 9.4.2) 
are to be obtained at approximately the same time as ECG measurements or blood sampling.  
When multiple assessments are scheduled for the same time point, the preferred order of 
completion should be as follows:  ECG, vital signs, and then blood sampling.
Any clinically significant findings from ECGs that result in a diagnosis and that occur after the 
patient receives the first dose of the investigational treatment should be reported to Lilly or its 
designee as an AE via eCRF.


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9.4.2. Vital Signs
For each patient, vital signs measurements should be conducted according to the Schedule of 
Activities (Section 2).
Sitting vital signs (BP, temperature, and pulse) will be measured after resting for a minimum of 
10 minutes at times indicated in the Schedule of Activities (Section 2) and preferably prior to 
blood sampling or administration of the investigational product. 
Any clinically significant findings from vital signs measurement that result in a diagnosis and 
that occur after the patient receives the first dose of study treatment should be reported to Lilly or 
its designee as an AE via eCRF.
9.4.2.1.
Hypertension
Patients who experience changes in BP (systolic BP at 160 mm Hg plus 20 mm Hg increase 
from baseline [Week 0; Visit 2]; and/or diastolic BP at 100 mm Hg plus 10 mm Hg increase 
from baseline) on 2 consecutive visits are to receive intervention for the management of 
hypertension.  Intervention may begin with lifestyle changes and could lead to the maximal 
intervention of withholding the dose of investigational product (see Section 8.1.2) and/or the 
introduction of antihypertensive agent(s) as medically appropriate.
9.4.3. Laboratory Tests
For each patient, laboratory tests (detailed in Appendix 2) should be conducted according to the 
Schedule of Activities (Section 2).
With the exception of laboratory test results that may unblind the study, Lilly or its designee will 
provide the investigator with the results of laboratory tests analyzed by a central vendor, if a 
central vendor is used for the clinical trial.  
Any clinically significant findings from laboratory tests that result in a diagnosis and that occur 
after the patient receives the first dose of investigational product should be reported to Lilly or its 
designee as an AE via eCRF.
9.4.3.1.
Pregnancy Testing
Pregnancy testing is to be performed only on women of child-bearing potential.
Serum pregnancy test will be done at screening only and will be performed centrally.  Patients 
determined to be pregnant will be discontinued from the study.
Patients will undergo urine pregnancy testing at the clinic during designated scheduled visits (see 
Section 2) which will be performed locally.  Result to be read prior to administration of 
investigational product.  The urine pregnancy test at Week 0 must be performed within 24 hours 
prior to exposure to the investigational product.
Urine pregnancy testing may be performed at additional time points during the treatment period 
and/or follow-up period, at the discretion of the investigator or if this is required by local 
regulations.  Patients determined to be pregnant will be discontinued from the study.
If a urine pregnancy test is not available, a serum pregnancy test is an acceptable alternative.  


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9.4.4. Immunogenicity Assessments
Samples from patients treated with secukinumab will not be analyzed for anti-secukinumab
antibodies.  These samples will be discarded at the end of the study.
At the visits and times specified in the Schedule of Activities (Section 2), venous blood samples 
will be collected to determine antibody production against mirikizumab.  To interpret the results 
of immunogenicity, a blood sample for PK analysis will be collected at the same time points.  All 
samples for immunogenicity should be taken predose when applicable.  With reports of
hypersensitivity events (immediate or non-immediate), additional samples will be collected as 
close to the onset of the event as possible, at the resolution of the event, and 30 days following 
resolution of the event.  Samples will be evaluated for PK, anti-drug antibodies (ADAs), and 
additional exploratory markers of hypersensitivity (see Section 7.8.2.1).  Instructions for the 
collection and handling of blood samples will be provided by the Sponsor.  The actual date and 
time (24-hour clock time) of each sampling will be recorded.  
Immunogenicity will be assessed by a validated assay designed to detect ADAs in the presence 
of mirikizumab at a laboratory approved by the Sponsor. 
 
 
  
 
 
 
 
 
Samples will be retained at a facility selected by the Sponsor for a maximum of 15 years after the 
last patient visit, or for a shorter period if local regulations and/or Ethical Review Boards (ERBs) 
require.  The duration allows the Sponsor to respond to future regulatory requests related to 
mirikizumab.  Any samples remaining after 15 years will be destroyed.
9.4.5. Other Tests 
9.4.5.1.
Physical Examination
Physical examination will be performed as specified in the Schedule of Activities (Section 2).  
One complete physical examination (excluding pelvic or rectal examinations), which includes
heart, lungs, peripheral lymph nodes, and abdomen, and visual examination of all skin areas 
(including genitalia and breast areas) will be performed at screening.  All physical examinations 
throughout the study should include a symptom-directed evaluation, as well as examination of 
heart, lungs, peripheral lymph nodes, and abdomen, and visual examination of all skin areas 
(including genitalia and breast areas).
CCI


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9.4.5.2.
Tuberculosis Screening
Screening:
Screening for active or latent TB infection (LTBI) will include a history, physical examination 
(Section 9.4.5.1), chest x-ray (Section 9.4.5.3) and, except as noted below under “Prior 
Treatment for LTBI or TB,” testing by an interferon-release assay (IGRA; QuantiFERON®-TB 
Gold or T-SPOT®) or a purified protein derivative (PPD) tuberculin skin test.
In people aged 5 years and over, IGRA is the preferred screening test for LTBI.  In countries 
where the PPD is available and is preferred (in the judgment of the investigator) as an alternative 
screening test for LTBI, that test may be used instead of an IGRA.  
Patients with documentation of a negative IGRA or PPD within 3 months before initial screening 
may not need to repeat TB testing at screening, based on the judgment of the investigator.  
Source documentation must include the original laboratory report (for IGRA) or a record of the 
size in millimeters of the induration response (for PPD).  A PPD recorded as negative without 
documenting the size of induration in millimeters, will not be acceptable and will require a retest.  
Monitoring:
After initial screening, tuberculosis testing will only be required based on clinical assessment of 
TB risk (symptoms/signs/known or suspected TB exposure), and according to local regulations
and/or local standard of care.  Such clinical assessments should be conducted periodically, at 
least every 4 months.
Interpretation of Screening Tests for LTBI
The QuantiFERON-TB Gold assay will be reported as negative, indeterminate, or positive.  The 
T-SPOT.TB assay will be reported as negative, borderline or positive.
A positive PPD is indicated by a skin test response 5 mm of induration documented between 
approximately 48 to 72 hours after test application (regardless of BCG vaccination history).  
Patients who do not return within 48 to 72 hours of test administration will be required to have 
the test repeated and then interpreted within this time frame.  
Patients with a diagnosis of LTBI, based on a positive IGRA test result or a positive PPD
response 5 mm of induration and no evidence of active TB, may be rescreened once after they 
meet the following requirements:

Have received at least 4 weeks of appropriate ongoing prophylactic therapy for LTBI as 
per local standard of care, and

Have no evidence of treatment hepatotoxicity (ALT and AST levels must remain 
≤2x ULN) upon retesting of serum ALT and AST levels before randomization.
Such patients must continue and complete appropriate LTBI therapy during the course of the 
study to remain eligible and must continue to meet all other inclusion and exclusion criteria for 
participation.


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Re-Testing and Confirmatory Testing
One retest is allowed for patients with an “indeterminate” QuantiFERON-TB Gold assay or 
“borderline” T-SPOT.TB assay.  Patients with 2 indeterminate QuantiFERON-TB Gold assays 
or 2 borderline T-SPOT.TB assays will be excluded.  
Confirmatory testing with an IGRA is allowed for selected patients who have a positive 
QuantiFERON-TB Gold assay, positive T-SPOT.TB assay, or positive PPD, who meet all of the 
following criteria and are assessed and documented by the investigator as likely to have a false-
positive test result:  no risk factors for LTBI, no risk factors for increased likelihood of 
progressing from LTBI to active TB, and have never resided in a high-burden country (detailed 
in Appendix 5).  If the confirmatory test is positive, the patient will be excluded from the study 
unless they complete at least 4 weeks of appropriate therapy for LTBI, based on national or 
international guidelines (as defined above), have no evidence of hepatotoxicity (ALT and AST 
levels must remain ≤2x ULN) upon retesting of serum ALT and AST levels after at least 4 weeks 
of LTBI treatment.  Such patients must continue and complete appropriate full course of LTBI 
therapy during the course of the study to remain eligible to participate.  If the confirmatory test is 
negative, these results will be discussed with the medical monitor in order to determine 
eligibility for the study.
Diagnosis of LTBI During Study
Patients diagnosed with LTBI during the study will temporarily discontinue the investigational 
product and will be offered treatment by the referring physician.  These patients can be 
considered for resumption of investigational product after completing the first 4 weeks of 
appropriate treatment, and no evidence of treatment hepatotoxicity, as described above.  These 
patients must continue with and complete a full course of treatment for LTBI in order to continue 
on investigational product.
Prior Treatment for LTBI or TB
Patients who have a documented history of completing an appropriate TB prophylaxis or 
treatment regimen (consistent with World Health Organization and/or United States Centers for 
Disease Control at the time of treatment), with no history of re-exposure since their treatments 
were completed and no evidence of active TB, are eligible to participate in the study; these 
patients should not undergo TB testing unless advised to do so based on local guidelines.  
Active TB 
Patients diagnosed with active TB at screening will be excluded. 
Patients diagnosed with active TB during the study will be discontinued and should be referred 
for appropriate treatment.
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.


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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
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+ will undergo periodic monitoring of HBV DNA per the 
Schedule of Activities (Section 2).  
In addition to the above, any enrolled patient who is HBcAb+ and who experiences an elevated 
ALT or AST level >3x 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 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.  
9.4.5.5.
Hepatitis C Screening
Patients who test positive for HCV antibody and have a positive confirmatory HCV RNA test at 
screening will be excluded.
Patients with a previous diagnosis of hepatitis C who have been treated with antiviral therapy 
and achieved a sustained virologic response may be eligible for inclusion in the study, provided 
they have no detectable RNA on the screening HCV RNA test for this protocol.  A sustained 
virologic response is defined as an undetectable HCV RNA level, 12 weeks after completion of a 
full, documented course of an approved antiviral therapy for HCV.  
Patients who have spontaneously cleared HCV infection, defined as (i) a positive HCV antibody 
test and (ii) a negative HCV RNA test, with no history of anti-HCV treatment, may be eligible 
for inclusion in the study, provided they have no detectable HCV RNA on screening for this 
study.
Any patient with a history of HCV infection who develops elevated ALT >3x ULN will be tested 
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Anyone diagnosed with hepatitis C during the study will be discontinued from the study and 
should receive appropriate follow-up medical care.
9.4.6. Safety Monitoring
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods.
In the event that safety monitoring uncovers an issue that needs to be addressed by unblinding at 
the group level, members of the DMC, consisting of members external to Lilly (see Section 
10.3.8), and/or the Lilly Global Patient Safety (GPS) Safety Internal Review Committee (SIRC), 
consisting of GPS reviewers outside the study team, when appropriate, can view unblinded data 
and conduct additional analyses of the unblinded safety data.  The SIRC and the GPS expedited 
reporting team can also unblind at the individual SAE case level, when appropriate.
9.4.6.1.
Hepatic Safety Monitoring
If a study patient experiences elevated ALT 3x ULN, ALP 2x ULN, or elevated TBL 
2x ULN, liver testing (Appendix 6) should be repeated within 3 to 5 days including ALT, AST, 
ALP, TBL, direct bilirubin, gamma-glutamyl transferase, and creatine kinase to confirm the 
abnormality and to determine if it is increasing or decreasing.  If the abnormality persists or 
worsens, clinical and laboratory monitoring should be initiated by the investigator and in 
consultation with the study medical monitor. Monitoring of ALT, AST, TBL, and ALP should 
continue until levels normalize or return to approximate baseline levels. 
Hepatic Safety Data Collection
Additional safety data should be collected via the eCRF if 1 or more of the following conditions 
occur: 

Elevation of serum ALT to 5x ULN on 2 or more consecutive blood tests

Elevated serum TBL to 2x ULN (except for cases of known Gilbert’s 
syndrome) 

Elevation of serum ALP to 2x ULN on 2 or more consecutive blood tests

Patient discontinued from treatment due to a hepatic event or abnormality of 
liver tests

Hepatic event considered to be a SAE
9.5.
Pharmacokinetics
At the visits and times specified in the Schedule of Activities (Section 2), venous blood samples 
will be collected to determine the serum concentrations of mirikizumab.
Instructions for the collection and handling of blood samples will be provided by the Sponsor.  
The actual date and time (24-hour clock time) of each sampling will be recorded.
Drug concentration information that may unblind the study will not be reported to investigative 
sites or blinded personnel.


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Bioanalytical samples collected to measure investigational product concentration will be retained 
for a maximum of 1 year following last patient visit for the study.
9.6.
Pharmacodynamics
Not applicable.
9.7.
Pharmacogenomics
9.7.1. Whole Blood Sample for Pharmacogenetic Research
A whole blood sample will be collected for pharmacogenetic analysis as specified in the 
Schedule of Activities (Section 2) where local regulations allow.
Samples will not be used to conduct unspecified disease or population genetic research either 
now or in the future.  Samples will be used to investigate variable response to mirikizumab and 
to investigate genetic variants thought to play a role in psoriasis.  Assessment of variable 
response may include evaluation of AEs or differences in efficacy.  
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the investigator site personnel.  
Samples will be retained at a facility selected by Lilly or its designee for a maximum of 15 years 
after the last patient visit for the study, or for a shorter period if local regulations and/or 
ERBs/investigational review boards impose shorter time limits. This retention period enables 
use of new technologies, response to regulatory questions, and investigation of variable response 
that may not be observed until later in the development of mirikizumab or after mirikizumab
becomes commercially available.
Molecular technologies are expected to improve during the 15-year storage period and therefore 
cannot be specifically named.  However, existing approaches include whole genome or exome 
sequencing, genome wide association studies, and candidate gene studies.  Regardless of the 
technology utilized, genotyping data generated will be used only for the specific research scope 
described in this section. 
9.8.
Biomarkers
Biomarker research is performed to address questions of relevance to drug disposition, target 
engagement, pharmacodynamics (PD), mechanism of action, variability of patient response 
(including safety), and clinical outcome.  Sample collection is incorporated into clinical studies 
to enable examination of these questions through measurement of biomolecules, including DNA, 
RNA, proteins, lipids, and other cellular elements.
Serum, plasma, whole blood RNA, and whole blood for epigenetics samples for 
nonpharmacogenetic biomarker research will be collected at the times specified in the Schedule 
of Activities (Section 2) where local regulations allow.
Samples will be used for research on the drug target, disease process, variable response to 
mirikizumab, pathways associated with psoriasis or associated diseases, mechanism of action of 


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mirikizumab, and/or research method or in validating diagnostic tools or assay(s) related to 
psoriasis or associated diseases.  
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the investigator site personnel.  
Samples will be retained at a facility selected by Lilly or its designee for a maximum 15 years 
after the last patient visit for the study, or for a shorter period if local regulations and ERBs 
impose shorter time limits.  This retention period enables use of new technologies, response to 
regulatory questions, and investigation of variable response that may not be observed until later 
in the development of mirikizumab or after mirikizumab becomes commercially available.
9.9.
Medical Resource Utilization and Health Economics
Health Economics and Medical Resource Utilization parameters will not be evaluated in this 
study.


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10. Statistical Considerations
10.1. Sample Size Determination
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 mirikizumab 
SC Q8W, 250 mg mirikizumab SC at Weeks 0, 4, 8, and 12, then 125 mg mirikizumab SC Q8W, 
300 mg secukinumab at Weeks 0, 1, 2, 3, and 4, followed by 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).
There are multiple primary endpoints in this study: the proportion of patients achieving a 90% 
improvement in PASI from baseline (PASI 90) and the proportion of patients with an sPGA (0,1) 
with at least a 2-point improvement from baseline, comparisons between mirikizumab and 
placebo (test of superiority), and comparison between mirikizumab and secukinumab (test of 
non-inferiority). The assumed PASI 90 responses are 70% for the mirikizumab arm 70% for the 
secukinumab arm, and 3% for the placebo arm.  The assumed sPGA 0 or 1 responses are 70% for 
the mirikizumab arm 70% for the secukinumab arm, and 5% for the placebo arm. Both PASI 90 
and sPGA (0,1) rates at Week 52 are estimated to be 75% for both mirikizumab dose groups, and 
65% for secukinumab group.  The assumptions for mirikizumab are based upon the results of the 
mirikizumab Phase 2 Study AMAF (Reich et al. 2017b) and review of historical clinical studies 
in psoriasis (Langley et al. 2014; Gordon et al. 2016; Blauvelt et al. 2017; Papp et al. 2017; 
Reich et al. 2017a). The assumptions for secukinumab was based upon 2 Phase 3 studies of 
secukinumab for psoriasis (Langley et al. 2014). 
With 888 patients in the mirikizumab group and 111 patients in the placebo group, the estimated
power is at least 99% to test superiority of mirikizumab to placebo on PASI 90 at Week 16, and 
on sPGA (0, 1) at Week 16, respectively, at alpha of 0.05 two-sided. With 888 patients in the 
mirikizumab group and 444 patients in the secukinumab group, the estimated power is at least 
90% to test noninferiority of mirikizumab to secukinumab at alpha of 0.025 one-sided with a 
noninferiority margin of 10% on PASI 90 at Week 16.  Similarly, the estimated power is least 
90% to test noninferiority of mirikizumab to secukinumab at alpha of 0.025 one-sided with a 
noninferiority margin of 10% on sPGA (0, 1) at Week 16.
In addition, with 444 patients in the 250 mg mirikizumab Q8W group, 444 patients in 125 mg 
mirikizumab Q8W group, and 444 patients in the secukinumab group, the study will have an 
estimated power of 90% to test superiority of 250 mg mirikizumab Q8W compared to 
secukinumab at alpha of 0.05 two-sided on PASI 90 at Week 52, and sPGA (0, 1) at Week 52,
respectively, as well as 90% power to test superiority of 125 mg mirikizumab Q8W compared to 
secukinumab at alpha of 0.05 two-sided on PASI 90 at Week 52, and sPGA (0, 1) at Week 52,
respectively.
10.2. Populations for Analyses
For purposes of analysis, the following populations are defined:


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Population
Description
ITT
All randomized patients, even if the patient does not take the assigned 
treatment, does not receive the correct treatment, or otherwise does not follow 
the protocol.  Patients will be analyzed according to the treatment to which 
they were assigned.  Unless otherwise noted, efficacy and health outcomes 
analyses for the induction period will be conducted on this population.
Induction Safety
All randomized patients who received at least 1 dose of study treatment.  
Safety analyses for the induction period will be conducted on this population.
All Active Treatment Safety
All randomized patients who received at least 1 dose of mirikizumab or 
secukinumab.
Abbreviation:  ITT = intent-to-treat.
Additional analysis populations will be described in the statistical analysis plan (SAP) as deemed 
appropriate.
10.3. Statistical Analyses
10.3.1. General Statistical Considerations
Statistical analysis of this study will be the responsibility of Lilly or its designee.
Any change to the data analysis methods described in the protocol will require an amendment 
only if it changes a principal feature of the protocol.  Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the clinical study report (CSR).  Additional exploratory analyses of the data will be conducted 
as deemed appropriate.
Efficacy analysis for induction and maintenance outcomes will be conducted on the intent-to-
treat (ITT) population as defined in Section 10.2.  The induction and maintenance safety analysis 
will be performed on the Induction and All Active Treatment safety populations, respectively.
Continuous data will be summarized in terms of the mean, standard deviation, minimum, 
maximum, median, and number of observations.  Categorical data will be summarized as 
frequency counts and percentages. Unless otherwise specified, all superiority tests will be 2-
sided with alpha of 0.05, and all non-inferiority tests will be 1-sided with alpha of 0.025. 
Multiple testing will be controlled as described in Section 10.3.1.2.
Unless otherwise specified, baseline for efficacy and health outcomes endpoints during both the 
Induction and Maintenance Periods will be defined as the last available value before the 
randomization, which in most cases will be the measure recorded at Week 0 (Visit 2). Detailed 
definitions of baseline for safety-related analyses will be described in the SAP. Unless otherwise 
specified, the statistical analysis models for the Induction Period and Maintenance Period will 
adjust for the covariates:  previous exposure to biologic therapy (yes/no), body weight (<100 kg 
or 100 kg), and geographic region (North America, Europe, or Other). 


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For assessments of the primary endpoints and other categorical efficacy and health outcomes 
endpoints, the Cochran–Mantel–Haenszel (CMH) test will be used to compare the treatment 
groups with the stratification factors mentioned above.  The CMH p-value will be provided.  In 
addition, the treatment difference in proportions will be provided along with the 95% 2-sided 
confidence interval estimate.
Treatment comparisons of continuous efficacy and health outcome variables with multiple post-
baseline measurements will be made using mixed-effects model for repeated measures (MMRM) 
analysis. Secondary analysis on key continuous efficacy and health outcome variables will also 
be performed using analysis of covariance (ANCOVA).  The log-rank test will be used to 
analyze the time to clinical response in the induction period.
Fisher’s exact test will be used for categorical safety data, including AEs, unless otherwise 
specified.  Laboratory analytes will be presented as mean changes from baseline and as incidence 
of shift between normal and abnormal states.  
10.3.1.1. Missing Data Imputation
The following methods for imputation of missing data will be used:

Non-Responder Imputation (NRI) for Binary Clinical Response:  Patients will be 
considered non-responders for the NRI analysis if they do not meet the clinical response 
criteria or have missing clinical response data at the analysis time point.  Randomized 
subjects without at least 1 postbaseline observation will also be defined as 
non-responders for the NRI analysis.

Mixed Model Repeated Measures (MMRM):  It will be the primary analysis method for 
longitudinal continuous measurements.  It assumes missing at random and the bias 
caused by missing data can be attenuated by modeling random effects using the within-
subject error correlation structure.
Additional missing data imputation methodologies, for example, modified baseline observation 
carried forward (mBOCF), may be considered as secondary analyses and will be fully detailed in 
the SAP.  By using mBOCF, for patients discontinuing study treatment due to an AE, the 
baseline observation will be carried forward to the corresponding primary endpoint for 
evaluation.  For patients discontinuing investigational product for any other reason, the last 
nonmissing postbaseline observation before discontinuation will be carried forward to the 
corresponding primary endpoint for evaluation.  
10.3.1.2. Multiple Comparisons/Multiplicity
The prespecified graphical multiple testing approach (Bretz et al. 2011) will be implemented to 
control the overall Type I error rate at 2-sided alpha of 0.05 for superiority tests and at 1-sided 
alpha of 0.025 for non-inferiority tests, for the hypotheses for the primary and major secondary 
endpoints.  The graphical approach is a closed testing procedure; hence it strongly controls the 
family-wise error rate across all endpoints (Alosh et al. 2014).
The Week 16 endpoints of sPGA (0,1) and PASI 90 represent a primary endpoint family.  The 
graphical testing scheme will sequentially test sPGA (0,1) first, followed by PASI 90 before 


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proceeding to test the major secondary endpoints. Details of the specific graphical testing 
scheme (including testing order, interrelationships, Type I error allocation for the major 
secondary endpoints, and the associated propagation) will be pre-specified in the SAPs prior to 
first unblinded analysis.
10.3.2. Treatment Group Comparability
10.3.2.1. Patient Disposition
A detailed description of patient disposition will be provided at the end of the study.
Patient disposition will be summarized for each treatment period.  Reasons for discontinuation 
from the study will be summarized.  
10.3.2.2. Patient Characteristics
Patient characteristics and baseline clinical measures will be summarized for each treatment 
period.  Baseline characteristics will include gender, age, age category, weight, race, geographic 
region, baseline disease severity, duration of disease, prior exposure to biologic therapy, previous 
nonbiologic systemic therapy, and previous biologic therapy.  Baseline clinical measurements 
will include sPGA score, PASI total score, BSA, PSSI, PSS symptom and sign total scores, 
PatGA, DLQI total score, SF-36 (PCS), and SF-36 (MCS).
10.3.2.3. Concomitant Therapy 
Previous and concomitant medications will be summarized for patients who enter each treatment 
period and will be presented using the latest version of the World Health Organization (WHO) 
drug dictionary. 
10.3.2.4. Treatment Compliance
Treatment compliance with investigational product will be summarized for patients who enter 
the Induction and Maintenance periods.  A patient will be considered as having missed the visit 
if he or she fails to attend for administration of the investigational product within the required 
treatment window as defined in the Schedule of Activities (Section 2).  Overall compliance with 
therapy is defined to be missing no more than 20% of the expected doses within the protocol-
defined dosing interval and not missing 2 consecutive doses.  The proportion of patients who 
demonstrate overall compliance during the Induction Period will be compared between treatment 
groups using Fisher’s exact test.
10.3.3. Efficacy Analyses
Primary and secondary analyses will be based on the ITT population as defined in Section 10.2.
Non-inferiority Margin and Analyses:
There is no universally accepted value for what is considered to be a clinically unimportant 
difference between 2 treatments in sPGA (0, 1) or PASI 90 response. Global regulatory 
guidance (EMA 2005 and FDA 2016 guidelines) indicate that selection of the non-inferiority 
margin is based upon a combination of statistical and clinical grounds.


I 6 T-M C -A M A J( b) Cli n i c al Pr ot o c ol
P a g e 7 4
L Y 3 0 7 4 8 2 8
F or acti ve c o ntr ol treat me nt sec u ki n u ma b, t he P A SI 9 0 res p o nse r ates of sec u ki n u ma b 3 0 0 m g 
Q 4 W d osi n g at Wee k 1 6 i n t he pi v otal P hase 3 st u dies were a p pr o xi matel y 7 1. 5 % a n d 7 0 % i n 
t he FI X T U R E a n d E R A S U R E st u dies, res pecti vel y ( La n gle y et al. 2 0 1 4 ).  I n t hese st u d y desi g ns, 
t here were n o place b o c o ntr ols be y o n d Wee k 1 2.  As t he P A SI 9 0 rates i n place b o patie nts were 
ver y  lo w a n d f e w fl uct uatio ns were o bser ve d i n t he i n d uct i on p hases of t hese st u dies, t he P A SI 
9 0 rates at Wee k 1 2 ( 1. 5 % a n d 1. 2 % i n t he FI X T U R E a n d E R A S U R E st u dies, res pect i vel y) were 
e xtra p olate d t o Wee k 1 6 t o pr o vi de esti mates of treat me nt effect wit h c o m paris o ns t o place b o at 
Wee k 1 6.  T he esti mate d treat me nt differe nces f or sec u ki n u ma b 3 0 0 m g Q 4 W ( wit h p lace b o) 
were a p pr o xi matel y 7 0 % a n d 6 9 % i n t he FI X T U R E a n d E R A S U R E st u dies. D ue t o t he 
c o nsiste nc y of treat me nt effect i n pi v otal st u dies of sec u ki n u ma b, a fi xe d NI mar gi n is pr o p ose d 
f or St u d y  A M AJ, i nstea d of bei n g base d o n t he s y nt hesis met h o d. 
T he NI m ar gi n o f 1 0 % o n P A SI 9 0 res p o nse is c o nsi dere d t o be s ufficie ntl y s mall t o be a 
cli nicall y u ni m p orta nt differe nce i n o utc o mes bet wee n mir i kiz u ma b a n d sec u ki n u ma b. It
re prese nts cli nical j u d g me nt a b o ut t he a m o u nt of t he acti ve c o ntr ol effect t hat m ust be retai ne d. 
Ass u mi n g t he o bser v e d treat me nt effects f or sec u ki n u ma b a n d place b o i n St u d y  A M AJ is si milar 
t o w hat has bee n o bser ve d i n hist orical st u dies, 7 0 %, t he pr o p ose d NI mar gi n o f 1 0 % is e x pecte d 
t o preser ve a s u bsta ntial fracti on ( 8 5. 7 %) of  t he sec u ki n u ma b effect. 
Si milarl y, a 1 0 % NI mar gi n will be use d f or t he ot her maj o r sec o n dar y e n d p o i nt s P G A ( 0, 1),
wi t h n o ni nferiori t y tests c o mpari n g mir i kiz u ma b a n d sec u ki n u ma b.
T here are se veral maj or sec o n dar y  or ot her sec o n dar y  e n d p oi nts t o be teste d f or NI bet wee n eac h 
mir i kiz u ma b d os e a n d sec u ki n u ma b at Wee k 2 4 a n d Wee k 5 2 ( Ta ble A M AJ. 5 ).  F or et hical 
reas o ns, patie nts will nee d t o be cr osse d o ver t o a n acti ve treat me nt after Wee k 1 6 i n ps oriasis 
st u dies.  T heref ore, n o hist orical d at a of place b o rates o n t hese e n d p oi nts were a vaila ble, a n d 
t here will be n o place b o gr o u p be yo n d Wee k 1 6 i n St u d y  AM AJ.  I nstea d, wi t h a reas o na ble a n d 
c o nser vati ve ass u m pt i on t hat pl ace b o rates at Wee k 1 6 c o ul d be carrie d o ver t o t he mai nte na nce 
p eri o d (at b ot h Wee k 2 4 a n d Wee k 5 2), t he treat me nt effects bet wee n sec u ki n u ma b a n d place b o 
at Wee k 2 4 a n d Wee k 5 2 o n t he e n d p oi nts are s u m marize d bel o w.  T he pr o p ose d NI mar gi n o f 
1 0 % i s s h o w n t o pr o vide hi g h rete nt i on rate of t he sec u ki n u ma b effect a n d t heref ore is 
s u g gesti ve of a cli nicall y u ni m p orta nt differe nce.


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Table AMAJ.5.
Proposed Noninferiority Margin for Various Major Secondary and 
Other Secondary Endpoints with Noninferiority Tests in 
Study I6T-MC-AMAJ
Estimated Treatment 
Effects for 
Secukinumaba
Proposed 
Noninferiority Margin
Proportion to Preserve 
Secukinumab Effect
PASI 90 at Week 24
70%
10%
85.7%
PASI 90 at Week 52
65%
10%
84.6%
PASI 100 at Week 52
40%
10%
75%
sPGA (0,1) at Week 52
70%
10%
85.7%
Abbreviations:  PASI = Psoriasis Area and Severity Index; sPGA = static Physician’s Global Assessment.
a
Assuming placebo rates carried from Week 16.
The null hypothesis will be rejected if the lower bound of the 1-sided 97.5% CI for the difference 
in proportions of responders on mirikizumab minus secukinumab is greater than the prespecified
NI margin (-10%), meaning mirikizumab will be deemed non-inferior to secukinumab. If the 
lower bound of the CI for the difference exceeds 0 (the corresponding p value will also be 
produced), mirikizumab will be deemed superior to secukinumab.
10.3.3.1. Primary Analyses
Treatment comparisons between mirikizumab and placebo in the proportion of patients achieving 
sPGA (0,1) with at least a 2-point improvement from baseline at Week 16 will be analyzed using 
the CMH method with NRI as described in Section 10.3.1. Also, treatment comparisons between 
mirikizumab and placebo in the proportion of patients achieving PASI 90 at Week 16 will be 
analyzed using the CMH method with NRI as described in Section 10.3.1.
10.3.3.2. Secondary Analyses
Protocol-defined secondary efficacy and health outcome endpoints of the trial are presented in 
Table AMAJ.2). Details of the analysis methods that will be utilized are provided in Section 
10.3.1. ).  As noted in Section 10.3.1.2, our graphical testing approach to multiplicity control will 
require both primary endpoints to be successful before proceeding to the major secondary 
endpoints.
Additional analyses of the secondary efficacy and health outcome endpoints may be considered 
and will be fully detailed in the SAP.  Additional endpoints may be pre-specified in the SAP.
10.3.3.3. Exploratory Analyses
Protocol-defined exploratory endpoints of the trial are presented in Table AMAJ.2.
Additional analyses of exploratory endpoints may be considered and will be fully detailed in the 
SAP. Additional endpoints including those involving assessments of the TSQM, EQ-5D-5L 
PSO, facial psoriasis, and the evaluation of the PSS psychometric properties will be pre-specified 
in the SAP.


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10.3.4. Safety Analyses
Safety assessments will include AEs, SAEs, AESIs, laboratory analytes, vital signs, QIDS-SR16, 
and C-SSRS.
The Induction Period safety analyses will compare mirikizumab to placebo using the methods 
described in Section 10.3.1).  The Maintenance Period safety analyses will summarize safety 
measures by treatment. 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities
(MedDRA) and summarized by system organ class, preferred term, severity, and relationship to 
investigational product.  A treatment-emergent adverse event (TEAE) is defined as an event that 
first occurred or worsened in severity after baseline.  For each event classification term, the 
number of patients experiencing a TEAE with that classification term will be tabulated.  
Treatment-related TEAEs are defined as events that are indicated by the investigator on the 
eCRF to be related to treatment.  If a patient reports the occurrence of a particular event more 
than once, the most severe of those events will be included in the summary tables of TEAEs, and 
the most severe of the most related of those events will be included in the summary tables of 
treatment-related events.  For events that are gender specific, the denominator and computation 
of the percentage will only include patients from the given gender.
Adverse events of special interest are defined in Section 9.2.3) and the analysis plan will be 
described in the Program Safety Analysis Plan and SAP.
10.3.5. Pharmacokinetic/Pharmacodynamic Analyses
The PK of mirikizumab will be characterized using visualization/graphical evaluations and 
mixed-effect (population PK) modeling approaches.  Various structural and error models will be 
evaluated.  Intrinsic factors (such as age, body weight, gender, immunogenicity) and extrinsic 
factors (such as co-medications) will be investigated to assess their influence on model 
parameters.  Model evaluation will include a visual predictive check.  Estimates of PK model 
parameters and covariate effects and corresponding 90% confidence intervals will be reported.
 
 
 
 
 
 
  
 
 
 
 
 
CCI


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Additional analyses may be conducted if they are deemed appropriate.  Data from this study may 
be combined with other study data, if appropriate.  Further details on PK and PK/PD analyses 
will be provided in the PK/PD analysis plan.
10.3.6. Evaluation of Immunogenicity 
The frequency and percentage of patients with pre-existing (baseline) ADA, ADA at any time 
post baseline, and with treatment-emergent ADA (TE-ADA) to mirikizumab will be tabulated.  
The frequency of neutralizing antibodies will also be tabulated.
The relationship between the presence of antibodies and the PK parameters and PD response,
including safety and efficacy to mirikizumab, will be assessed.
10.3.7. Other Analyses
10.3.7.1. Subgroup Analyses 
Subgroup analyses will be conducted for sPGA (0,1) and PASI 90 at Week 16 (NRI) using the 
Induction ITT population.
Subgroups to be evaluated will include the following:

Patient Demographics and Characteristics Subgroups
o
Gender, age, body weight, BMI, race/ethnicity, age at onset of psoriasis

Geographic Regions

Baseline Severity of Disease Subgroups, including:
o
Disease duration, sPGA, and PASI

Previous Psoriasis Therapy Subgroups, including:
o
Naïve to conventional systemic and biologic therapies
o
Previous use of systemic or phototherapies
o
Previous use biologic psoriasis therapies
o
Prior failure of biologic psoriasis therapies
o
Prior failure of systemic agent or contraindication

Psoriasis Involvement Subgroups

Concomitant Medications Subgroups

Anti-Mirikizumab Antibody Status
A detailed description of the subgroup variables will be provided in the SAP. Additional 
subgroups and analyses may be performed as deemed appropriate and necessary.
10.3.7.2. Psoriasis Symptoms Scale Psychometric Analysis
Psychometric analysis of PSS will be defined in a separate health outcomes SAP.  The analyses 
will evaluate the validity, responsiveness, and interpretability of the PSS.
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10.3.8. Interim Analyses
One DMC consisting of members external to Lilly will be established for interim safety 
monitoring across all Phase 3 trials in patients with psoriasis.  This committee will consist of a 
minimum of 3 members including a physician with expertise in dermatology, a statistician, and 
an additional clinician(s).  No member of the DMC may have contact with study sites.  A 
Statistical Analysis Center (SAC) will prepare and provide unblinded safety data to the DMC.  
The SAC members may be Lilly employees or from third-party organizations designated by Lilly.  
However, they will be external to the study team and will have no contact with sites and no 
privileges to influence change in the ongoing study. The study team will not have access to the 
unblinded data.  The purpose of the DMC is to advise Lilly regarding continuing patient safety; 
however, the DMC may request key efficacy data to put safety observations into context and to 
confirm a reasonable benefit/risk profile for ongoing patients in the study.  Hence, there will be 
no alpha adjustment for these interim assessments.  Study sites will receive information about 
interim assessments only if they need to know for the safety of their patients.  This committee 
will make recommendations as to whether it is scientifically and ethically appropriate to continue 
enrollment, discontinue a treatment group, or discontinue the study.  Details outlining the roles 
and responsibilities of the DMC will be finalized in the DMC charter and an associated DMC 
analysis plan prior to the first unblinded assessment. 
To support regulatory submission, an analysis including the primary and major secondary 
endpoints will be conducted after all patients complete Week 52 or discontinue early. If all 
patients have entered the long-term extension Study I6T-MC-AMAH, or discontinued the study 
early, this analysis is deemed as the final analysis.  Otherwise, this analysis will be an interim 
analysis for the primary outcome; the final analysis will be conducted after all patients have 
entered the long-term extension Study I6T-MC-AMAH, or have completed the follow-up period 
of Study AMAJ, or discontinued the study early.
In addition, a limited number of pre-identified internal Lilly personnel that are not in contact 
with clinical sites may gain access to unblinded PK/PD data, as specified in the unblinding plan, 
prior to the Week 52 database lock, in order to initiate the final population PK/PD model 
development processes. Unblinding details will be provided in the unblinding plan.


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11.
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_Product_Information/human/003729/WC500183129.pdf.  Accessed February 07, 2018.
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12.
Appendices


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Appendix 1.
Abbreviations and Definitions
Term
Definition
AIDS
acquired immune deficiency syndrome
ADA
anti-drug antibody
AE
adverse event:  Any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment.  An adverse event can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the medicinal (investigational) product.
AESI
adverse event of special interest
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
blinding/masking
A single-blind study is one in which the investigator and/or his staff are aware of the 
treatment but the patient is not, or vice versa, or when the Sponsor is aware of the 
treatment but the investigator and/his staff and the patient are not.
A double-blind study is one in which neither the patient nor any of the investigator or 
Sponsor staff who are involved in the treatment or clinical evaluation of the subjects are 
aware of the treatment received.
BCG
Bacillus Calmette-Guerin
BP
blood pressure
BSA
body surface area
CIOMS
Council for International Organizations of Medical Sciences
CMH
Cochran-Mantel-Haenszel
complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
compliance
Adherence to all study-related, good clinical practice (GCP), and applicable regulatory 
requirements.
CRF
case report form


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CSR
clinical study report
C-SSRS
Columbia-Suicide Severity Rating Scale
CXR
chest x-ray
DLQI
Dermatology Life Quality Index
DMC
data monitoring committee
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eCOA
electronic clinical outcome assessments
eCRF
electronic case report form
EMA
European Medicines Agency
enroll
The act of assigning a patient to a treatment.  Patients who are enrolled in the study are 
those who have been assigned to a treatment.
enter
Patients entered into a study are those who sign the informed consent form directly or 
through their legally acceptable representatives.
EQ-5D-5L-PSO
European Quality of Life–5 Dimensions–5 Levels–Psoriasis
ERB
Ethical Review Board
ETV
early termination visit
FDA
United States Food and Drug Administration
GCP
good clinical practice
GMP
Good Manufacturing Practice
GPS
Global Patient Safety
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HRQoL
health-related quality of life


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IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IGRA
interferon-release assay
IL-23
interleukin-23
Informed consent
A process by which a patient voluntarily confirms his or her willingness to participate 
in a particular study, after having been informed of all aspects of the study that are 
relevant to the patient’s decision to participate.  Informed consent is documented by 
means of a written, signed and dated informed consent form.
interim analysis
An interim analysis is an analysis of clinical study data, separated into treatment groups, 
that is conducted before the final reporting database is created/locked.
investigational 
product
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form.
INR
international normalized ratio
ITT
intention to treat:  The principle that asserts that the effect of a treatment policy can be 
best assessed by evaluating on the basis of the intention to treat a patient (that is, the 
planned treatment regimen) rather than the actual treatment given.  It has the 
consequence that patients allocated to a treatment group should be followed up, 
assessed, and analyzed as members of that group irrespective of their compliance to the 
planned course of treatment.
IV
intravenous
IWRS
interactive web-response system
LTBI
latent tuberculosis infection
mBOCF
modified baseline observation carried forward
MCID
minimal clinically important difference
MCS
mental component summary of the SF-36
medical monitor
Individual responsible for the medical conduct of the study.  Responsibilities of the 
medical monitor may be performed by a physician, clinical research scientist, global 
safety physician, or other medical officer.
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
mixed-effects model for repeated measures
MOS
margin of safety


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NAPSI
Nail Psoriasis Severity Index
NOAEL
no-observed-adverse-effect-level
NRI
non-responder imputation
NRS
numeric rating scale
PA
posterior-anterior (chest x-ray)
PASI
Psoriasis Area and Severity Index
PatGA
Patient’s Global Assessment Psoriasis
PCS
physical component summary of the SF-36
PD
pharmacodynamics(s)
PK
pharmacokinetic(s)
PK/PD
pharmacokinetics/pharmacodynamics
PPASI
Palmoplantar Psoriasis Severity Index
PPD
purified protein derivative (skin test)
PSS
Psoriasis Symptoms Scale
PSSI
Psoriasis Scalp Severity Index
PUVA
psoralen and ultraviolet A
Q4W
every 4 weeks
Q8W
every 8 weeks
QIDS-SR16
16-item Quick Inventory of Depressive Symptomatology
RNA
ribonucleic acid
SAC
Statistical Analysis Center
SAE
serious adverse event
SAP
statistical analysis plan
SC
subcutaneous
screen
The act of determining if an individual meets minimum requirements to become part of 
a pool of potential candidates for participation in a clinical study. 
SF-36
Medical Outcomes Study 36-item Short-Form Health Survey
SIRC
Safety Internal Review Committee


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sPGA
static Physician’s Global Assessment
SUSARs
suspected unexpected serious adverse reactions
TB
tuberculosis
TBL
total bilirubin level
TE-ADA
treatment-emergent anti-drug antibody
TEAE
Treatment-emergent adverse event:  An untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative 
to the pretreatment state, and does not necessarily have to have a causal relationship 
with this treatment.
Th
T helper
TNF
tumor necrosis factor
TSQM
Treatment Satisfaction Questionnaire for Medication
ULN
upper limit of normal
WBC
white blood cell
WHO
World Health Organization
WPAI-PSO
Work Productivity and Activity Impairment Questionnaire: Psoriasis


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Appendix 2.
Clinical Laboratory Tests
Clinical Laboratory Tests
Hematologya
Clinical Chemistrya
Other
Hemoglobin
Serum Concentrations of:
Human immunodeficiency virus (HIV)b
Hematocrit
Sodium
Hepatitis B surface antigen (HBsAg)b
Erythrocyte count (RBC)
Potassium
Hepatitis B core antibody (HBcAb)b
Mean cell volume
Total bilirubin
Hepatitis B surface antibody (HBsAb)b
Mean cell hemoglobin
Total protein
HBV DNA testc
Mean cell hemoglobin 
concentration
Direct bilirubin
Hepatitis C antibodyb
Leukocytes (WBC)
Alkaline phosphatase (ALP)
HCV RNA testc
Cell morphology
Alanine aminotransferase (ALT)
Pregnancy Test (females only)
Absolute Counts and 
Percentage of:
Aspartate aminotransferase (AST)
Serumb
Neutrophils, segmented
Gamma-glutamyl transferase (GGT)
Urine (assayed locally by clinical 
study site)
Lymphocytes
Blood urea nitrogen (BUN)
Follicle-stimulating hormone (FSH)b
Monocytes
Creatinine
PPD or QuantiFERON®-TB Gold test 
or T-SPOT®.TB testd
Eosinophils
Uric acid
Exploratory storage samples (DNA)
Basophils
Calcium
Exploratory storage samples (serum, 
plasma, whole blood, RNA)
Absolute Counts of:
Glucose
Anti-mirikizumab antibodies 
(immunogenicity)a
Platelets
Albumin
Serum mirikizumab concentration 
(PK)a
Cholesterol (total)
Tryptasea
Urinalysisa,
Triglycerides
Complement panel (C3 and C4)a
Specific gravity
Creatine kinase (CK)
Cytokine panela
pH
High-sensitivity C-reactive protein 
(hsCRP)
Protein
Lipid Panel (fasting)
Glucose
Low-density lipoprotein (LDL)
Ketones
High-density lipoprotein (HDL)
Bilirubin
Very-low-density lipoprotein (VLDL)
Urobilinogen
Blood
Nitrite
Urine leukocyte esterase
Microscopic examination of 
sediment
Abbreviations:  DNA = deoxyribonucleic acid; HBV = hepatitis B virus; HCV = hepatitis C virus; 
PK = pharmacokinetic(s); PPD = purified protein derivative (skin test); RBC = red blood cells; 
RNA = ribonucleic acid; TB = tuberculosis; WBC = white blood cells.
a
Unscheduled hematology or blood chemistry panels may be performed at the discretion of the investigator. If a 
patient develops an acute hypersensitivity event after administration of IP, blood samples will be collected for 
pharmacokinetic, immunogenicity, and exploratory hypersensitivity analyses.
b
Performed at screening only.


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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.
d
TB testing will be performed locally using an interferon-release assay (IGRA, for example 
QuantiFERON®-TB Gold test or T-SPOT.TB®) or a PPD tuberculin skin test. If PPD test is performed, patients 
will return 2 to 3 days afterwards to have their PPD test read.


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Appendix 3.
Study Governance Considerations


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Appendix 3.1. Regulatory and Ethical Considerations, Including the 
Informed Consent Process
Appendix 3.1.1.
Informed Consent
The investigator is responsible for:

Ensuring that the patient understands the nature of the study, the potential 
risks and benefits of participating in the study, and that their participation is 
voluntary.

Ensuring that informed consent is given by each patient or legal 
representative.  This includes obtaining the appropriate signatures and dates 
on the informed consent form (ICF) prior to the performance of any protocol 
procedures and prior to the administration of investigational product.

Answering any questions the patient may have throughout the study and 
sharing in a timely manner any new information that may be relevant to the 
patient’s willingness to continue his or her participation in the study.

Ensuring that a copy of the ICF is provided to the participant or the 
participant’s legal representative and is kept on file.

Ensuring that the medical record includes a statement that written informed 
consent was obtained before the participant was enrolled in the study and the 
date the written consent was obtained. The authorized person obtaining the 
informed consent must also sign the ICF. 
Appendix 3.1.2.
Recruitment
Lilly or its designee is responsible for the central recruitment strategy for patients.  Individual 
investigators may have additional local requirements or processes.
Appendix 3.1.3.
Ethical Review
The investigator or an appropriate local representative must give assurance that the ethical 
review board (ERB) was properly constituted and convened as required by International Council
for Harmonisation (ICH) guidelines and other applicable laws and regulations.
Documentation of ERB approval of the protocol and the ICF must be provided to Lilly before the 
study may begin at the investigative site(s).  Lilly or its representatives must approve the ICF, 
including any changes made by the ERBs, before it is used at the investigative site(s).  All ICFs 
must be compliant with the ICH guideline on Good Clinical Practice (GCP).
The study site’s ERB(s) should be provided with the following:

The protocol and related amendments and addenda, current IB and updates 
during the course of the study

Informed consent form 

Other relevant documents (for example, curricula vitae, advertisements)


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Appendix 3.1.4.
Regulatory Considerations
This study will be conducted in accordance with the protocol and with the:

Consensus ethics principles derived from international ethics guidelines, 
including the Declaration of Helsinki and Council for International Organizations
of Medical Sciences (CIOMS) International Ethical Guidelines

Applicable ICH GCP Guidelines

Applicable laws and regulations
Some of the obligations of the Sponsor will be assigned to a third party.
Appendix 3.1.5.
Investigator Information
Physicians with a specialty in dermatology or other relevant specialties with appropriate 
experience with diagnosis and treatment of patients with psoriasis will participate as 
investigators in this clinical trial.
Appendix 3.1.6.
Protocol Signatures
The Sponsor’s responsible medical officer and statistician will approve the protocol, confirming 
that, to the best of his or her knowledge, the protocol accurately describes the planned design and 
conduct of the study.
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to a Lilly representative.
Appendix 3.1.7.
Final Report Signature
The clinical study report (CSR) coordinating investigator will sign the final CSR for this study, 
indicating agreement that, to the best of his or her knowledge, the report accurately describes the 
conduct and results of the study.
The CSR coordinating investigator will be selected by the Sponsor.  If this investigator is unable 
to fulfill this function, another investigator will be chosen by Lilly to serve as the CSR 
coordinating investigator.
The Sponsor’s responsible medical officer and statistician will approve the final CSR for this 
study, confirming that, to the best of his or her knowledge, the report accurately describes the 
conduct and results of the study.
Appendix 3.2.
Data Quality Assurance
To ensure accurate, complete, and reliable data, Lilly or its representatives will do the following:

Provide instructional material to the study sites, as appropriate

Sponsor start-up training to instruct the investigators and study coordinators.  This 
training will give instruction on the protocol, the completion of the case report 
forms (CRFs), and study procedures.


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
Make periodic visits to the study site

Be available for consultation and stay in contact with the study site personnel by 
mail, telephone, and/or fax

Review and evaluate CRF data and use standard computer edits to detect errors in 
data collection

Conduct a quality review of the database
In addition, Lilly or its representatives will periodically check a sample of the patient data 
recorded against source documents at the study site.  The study may be audited by Lilly or its 
representatives, and/or regulatory agencies at any time.  Investigators will be given notice before 
an audit occurs.
The investigator will keep records of all original source data.  This might include laboratory 
tests, medical records, and clinical notes.  If requested, the investigator will provide the Sponsor, 
applicable regulatory agencies, and applicable ERBs with direct access to original source 
documents.
Appendix 3.2.1.
Data Capture System
An electronic case report form (eCRF) system will be used in this study.  The site maintains a 
separate source for the data entered by the site into the Sponsor-provided eCRF system.  Case 
report form data will be encoded and stored in a clinical trial database.  
Electronic clinical outcome assessments (eCOA) measures (questionnaires, scales, self-reported 
diary data, etc.) will be collected by the patients and site personnel at the time that the 
information is obtained.  In these instances, where there is no prior written or electronic source 
data at the site, the eCOA data record will serve as the source.  The eCOA data will be stored at a 
third party site.  Investigator sites will have continuous access to the source documents during 
the study and will receive an archival copy at the end of the study for retention.  Any data for 
which the eCOA instrument record will serve to collect source data will be identified and 
documented by each site in that site’s study file.
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system.  Data will subsequently be transferred from the central 
vendor to the Lilly data warehouse.
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.
Appendix 3.3.
Study and Site Closure
Appendix 3.3.1.
Discontinuation of Study Sites
Study site participation may be discontinued if Lilly or its designee, the investigator, or the ERB 
of the study site judges it necessary for medical, safety, regulatory, or other reasons consistent 
with applicable laws, regulations, and GCP.


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Appendix 3.3.2.
Discontinuation of the Study
The study will be discontinued if Lilly or its designee judges it necessary for medical, safety, 
regulatory, or other reasons consistent with applicable laws, regulations, and GCP.
Appendix 3.4.
Publication Policy
The publication policy for Study I6T-MC-AMAJ is described in the letters of agreement between 
the Sponsor and the investigators and institutions.


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Appendix 4.
Examples of Infections That May Be 
Considered Opportunistic in the Setting of Biologic 
Therapy


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Bacterial
Bartonellosis (disseminated disease only)
Campylobacteriosis (invasive disease only)
Legionellosis
Listeria monocytogenes (invasive disease only)
Nocardiosis
Tuberculosis
Non-tuberculous mycobacterial disease 
Salmonellosis (invasive disease only) 
Shigellosis (invasive disease only)
Vibriosis (invasive disease due to Vibrio vulnificus)
Viral
BK virus disease including polyomavirus-associated nephropathy
Cytomegalovirus disease
Hepatitis B virus reactivation
Hepatitis C virus progression
Herpes simplex (invasive disease only)
Herpes zoster (any form)
Post-transplant lymphoproliferative disorder (Epstein-Barr virus)
Progressive multifocal leukoencephalopathy (PML), John Cunningham (JC) virus [excluded from the study]
Fungal
Aspergillosis (invasive disease only)
Blastomycosis
Candidiasis (invasive disease or pharyngeal)
Coccidioidomycosis
Cryptococcosis
Histoplasmosis
Paracoccidioides infections
Penicillium marneffei
Pneumocystis jirovecii (formerly Pneumocystis carinii)
Sporothrix schenckii
Other invasive fungi:  Mucormycosis (zygomycosis) (Rhizopus, Mucor and Lichtheimia), 
Scedosporium/Pseudallescheria boydii, Fusarium
Protozoan
Leishmaniasis (visceral only)
Microsporidiosis
Toxoplasmosis
Trypanosoma cruzi infection (Chagas’ disease) (disseminated disease only)
Source:  Adapted from Winthrop et al. (2015).
This table is provided to aid the investigator in recognizing infections that may be considered opportunistic in the 
context of biologic therapy, for the purposes of Exclusion Criterion [16].  This list is not exhaustive.  
Investigators should use their clinical judgment, as well as discussion with the Lilly-designated medical monitor, 
in determining if other infections may be considered opportunistic, for the purposes of Exclusion Criterion [16].  
Winthrop et al. (2015) consider tuberculosis (TB) and non-TB mycobacterial disease to be opportunistic infections 
in the context of biologic therapy.  See Section 9.4.5.2 for the approach to screening for latent TB infection 
within the study.


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Appendix 5.
Risk Factors for Latent Tuberculosis 
Infection


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Risk Factors for Latent Tuberculosis Infection
Household contact or recent exposure to an active case
Mycobacterial laboratory personnel
Birth or residency in a high burden country (>20/100,000)
Residents and employees of high risk congregate settings, for example, prisons, homelessness, intravenous drug use
Source:  Adapted from Horsburgh and Rubin (2011) and Lewinsohn et al. (2017).
Risk Factors for Increased Likelihood of Progression from LTBI to Active TB
Household contact or close contact with an active case
HIV
Radiographic evidence of old, healed TB that was not treated
Silicosis
Treatment with 15 mg prednisone (or equivalent) per day
Children <5 years of age
Chronic renal failure
Treatment with an anti-TNF antibody
Poorly controlled diabetes
Intravenous drug use
Weight 10% below normal
Smoking
Abbreviations:  HIV = human immunodeficiency virus; LTBI = latent tuberculosis infection; TB = tuberculosis; 
TNF = tumor necrosis factor.
Source:  Adapted from Horsburgh and Rubin (2011) and Lewinsohn et al. (2017).
World Health Organization List of High Burden Countries
Angola
India
Peru
Azerbaijan
Indonesia
Philippines
Bangladesh
Kenya
Russian Federation
Belarus
Kazakhstan
Sierra Leone
Botswana
Democratic People’s Republic of Korea
Somalia
Brazil
Kyrgyzstan
South Africa
Cambodia
Lesotho
Swaziland
Cameroon
Liberia
Tajikistan
Central African Republic
Malawi
United Republic of Tanzania
Chad
Moldova
Thailand
China
Mozambique
Uganda
Congo
Myanmar
Ukraine
Democratic Republic of the Congo
Namibia
Uzbekistan
Ethiopia
Nigeria
Vietnam
Ghana
Pakistan
Zambia
Guinea-Bissau
Papua New Guinea
Zimbabwe
Source:  WHO (2015).


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Appendix 6.
Hepatic Monitoring Tests for Treatment-
Emergent Abnormality
Selected tests may be obtained in the event of a treatment-emergent hepatic abnormality and may 
be required in follow-up with patients in consultation with the Lilly-designated medical monitor.
Hepatic Monitoring Tests
Hepatic Hematologya
Haptoglobina
Hemoglobin
Hematocrit
Hepatic Coagulationa
Red blood cells (RBC)
Prothrombin Time
White blood cells (WBC)
Prothrombin Time, INR
Neutrophils, segmented
Lymphocytes
Hepatic Serologiesa,b
Monocytes
Hepatitis A antibody, total
Eosinophils
Hepatitis A antibody, IgM
Basophils
Hepatitis B surface antigen
Platelets
Hepatitis B surface antibody
Hepatitis B Core antibody
Hepatic Chemistrya
Hepatitis C antibody
Total bilirubin
Hepatitis E antibody, IgG
Direct bilirubin
Hepatitis E antibody, IgM
Alkaline phosphatase (ALP)
Alanine aminotransferase (ALT)
Anti-nuclear antibodya
Aspartate aminotransferase (AST)
Gamma-glutamyl transferase (GGT)
Alkaline Phosphatase Isoenzymesa
Creatine phosphokinase (CPK)
Anti-smooth muscle antibody (or anti-actin 
antibody)a
Abbreviations:  Ig = immunoglobulin; INR = international normalized ratio.
a
Assayed by Lilly-designated or local laboratory.
b
Reflex/confirmation dependent on regulatory requirements and/or testing availability.


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Appendix 7.
Protocol Amendment I6T-MC-AMAJ(b)
Summary: 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
Overview
Protocol I6T-MC-AMAJ (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]) has been amended.  This amendment is 
considered to be substantial based on the criteria set forth in Article 10(a) of Directive 
2001/20/EC of the European Parliament and the Council of the European Union.  The new 
protocol is indicated by amendment (b) and will be used to conduct the study in place of any 
preceding version of the protocol.  The primary changes in this amendment are:

The primary objective of assessing mirikizumab noninferiority to secukinumab at 
Week 16 has been moved to major secondary objectives.

The major secondary objective of assessing mirikizumab induction dosing superiority 
compared to placebo at Week 4 has been moved to other secondary objectives.

The major secondary endpoint of proportion of patients achieving PASI 90 at Week 24
has been moved to other secondary endpoints.

The endpoint of proportion of patients achieving PASI 100 has been added to 
maintenance dosing Week 52 major secondary endpoints.

Language in the statistical analyses sections has been corrected and updated.
The overall changes and rationale for the changes made to this protocol are described in the 
following table:


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Amendment Summary for Protocol I6T-MC-AMAJ Amendment(b)
Section # and Name
Description of Change
Brief Rationale
Global
Global
Various typos fixed and clarifications made
Section 1
Section 1. Protocol Synopsis
1.
Moved primary objective of noninferiority 
at Week 16 to major secondary objectives
2.
Moved major secondary objective at Week 
4 to other secondary objectives
3.
Moved major secondary objective
endpoint of PASI 90 at Week 24 to other 
secondary objectives endpoints.
4.
Added endpoint of proportion of patients 
achieving PASI 100 at Week 52 for 
superiority objective
5.
“the Cochran–Mantel–Haenszel (CMH) 
chi-square test along with Non-Responder 
Imputation (NRI) will be used to compare 
the treatment groups.  The CMH 
stratification factors will be the same as 
those used in the stratified randomization 
scheme.  The CMH chi-square p-value will 
be provided.”
6.
“the absolute treatment difference in 
proportions will be provided along with 
the 95% 2-sided confidence interval 
estimate.”
1-4. These changes are based on new
information about head-to-head trials with 
IL-17 inhibitors. Changing the objectives 
as described allows Study AMAJ to 
address the potential advantages or 
differentiating attributes of mirikizumab, 
especially during the longer-term 
treatment stages (Week 52), as it 
compares to an IL-17 inhibitor 
(secukinumab).
5.
Error in original protocol.
6.
The word “absolute” is not appropriate in 
this context.


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Amendment Summary for Protocol I6T-MC-AMAJ Amendment(b)
Section 4
Section 4. Objectives and Endpoints
Updated Table AMAJ.2
To match changes made to protocol synopsis 
objectives and endpoints
Section 10
Section 10.3.1. General Statistical Considerations
Corrected usage of statistical analysis terminology
To match changes made to protocol synopsis 
statistical analysis
Section 10.3.1.1. Missing Data Imputation
Corrected usage of statistical analysis terminology
Corrected usage of statistical analysis terminology
Section 10.3.3. Efficacy Analyses
1.
Updated noninferiority margin text
2.
Updated Table AMAJ.5
1.
Noninferiority margin primary objective 
moved to major secondary objective

Major secondary noninferiority 
objective moved to other 
secondary objectives
2.
Table title updated to reflect the inclusion 
of major and other secondary endpoints 
with noninferiority tests
Section 10.3.8. Interim Analyses
“Otherwise, this analysis will be an interim 
analysis for the primary outcome; the final analysis 
will be conducted after all patients have entered the 
long-term extension Study I6T-MC-AMAH, or have 
completed the follow-up period of Study AMAJ, or 
discontinued the study early.”
Minor clarification of interim analysis
Abbreviations:  IL-17 = interleukin 17; PASI = Psoriasis Area and Severity Index; PASI 90 = ≥90% improvement in PASI from baseline; PASI 100 = ≥100% 
improvement in PASI from baseline.


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Revised Protocol Sections
Note:
Deletions have been identified by strikethroughs.
Additions have been identified by the use of underscore.
Section 1. Protocol Synopsis
Objective(s)/Endpoints:  
Objectives
Endpoints
Primarya,b
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to high levels of 
clinical response
At Week 16:

Proportion of patients with an sPGA (0,1) with 
at least a 2-point improvement from baseline

Proportion of patients achieving a 90% 
improvement in PASI from baseline (PASI 90)
To assess whether mirikizumab induction dosing is 
noninferior to secukinumab with respect to high levels 
of clinical response
At Week 16:

Proportion of patients with an sPGA (0,1) with 
at least a 2-point improvement from baseline

Proportion of patients achieving PASI 90
Major Secondarya,b
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to an early, clinically 
meaningful response
At Week 4:

Proportion of patients achieving a 75% 
improvement in PASI (PASI 75)
To assess whether mirikizumab induction dosing 
is superior to placebo with respect to clinically 
meaningful response and highest levels of 
clinical response
At Week 16:

Proportion of patients achieving a 75% 
improvement in PASI (PASI 75)

Proportion of patients achieving a 100% 
improvement in PASI from baseline (PASI 100)
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to body surface area 
(BSA) affected by psoriasis
At Week 16:

Proportion of patients with ≤1% of BSA with 
psoriasis involvement
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to patient-reported 
outcomes
At Week 16:

Proportion of patients with a PSS symptoms 
score of 0 (free of itch, pain, stinging, and 
burning) in those with a PSS symptoms score 
1 at baseline

Proportion of patients achieving a DLQI total 
score of (0,1) with at least a 5-point 
improvement (reduction) from baseline in 
patients with a baseline DLQI total score 5


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To assess whether mirikizumab induction dosing is 
noninferior to secukinumab with respect to high levels 
of clinical response
At Week 16:

Proportion of patients with an sPGA (0,1) with 
at least a 2-point improvement from baseline

Proportion of patients achieving PASI 90
To assess whether mirikizumab induction dosing is 
noninferior to secukinumab with respect to high levels 
of clinical response
At Week 24:

Proportion of patients achieving PASI 90
To assess whether 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W maintenance dosing is
noninferior to secukinumab with respect to high and 
highest levels of clinical response
At Week 52:

Proportion of patients achieving sPGA (0,1)

Proportion of patients achieving PASI 90

Proportion of patients achieving PASI 100
To assess whether 250 mg mirikizumab maintenance
Q8W and 125 mg mirikizumab Q8W dosing is
superior to secukinumab with respect to high levels 
of clinical response
At Week 52:

Proportion of patients achieving sPGA (0,1)

Proportion of patients achieving PASI 90

Proportion of patients achieving PASI 100
Other Secondaryb
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to an early, clinically 
meaningful response
To compare mirikizumab to placebo with respect to 
clinical response and time to clinical response during 
the induction dosing period, and with respect to patient-
reported outcomes during the induction dosing period
At Week 4:

Proportion of patients achieving a 75% 
improvement in PASI (PASI 75)
At Week 16 and various time points over the first 
16 weeks of dosing:

Proportion of patients achieving PASI 90

Change from baseline in PPASI total score in 
patients with palmoplantar involvement 
at baseline

Change in PSSI total score in patients with 
scalp involvement at baseline

Change from baseline in NAPSI total score in 
patients with fingernail involvement 
at baseline

Change from baseline on the SF-36 physical 
component summary (PCS) and mental 
component summary (MCS) 

Change from baseline on PatGA of disease 
severity

Change from baseline for the WPAI PSO 
scores (Absenteeism, Presenteeism, Work 
Productivity Loss, and Activity Impairment)

Change from baseline in QIDS-SR16 total 
score in those with a baseline QIDS-SR16 
total score 11

Proportion of patients achieving a DLQI total 
score of (0,1) with at least a 5-point 
improvement (reduction) from baseline in 
patients with a baseline DLQI total score 5


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
Proportion of patients achieving DLQI (0,1) 
with DLQI baseline score >1
To compare mirikizumab to secukinumab with respect 
to clinical response and time to clinical response during 
the induction dosing period, and with respect to patient-
reported outcomes during the induction dosing period
At Week 16 and various time points over the first 
16 weeks of dosing:

Proportion of patients achieving PASI 90 
To assess whether 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W maintenance dosing is
noninferior to secukinumab with respect to high levels 
of clinical response
At Week 24:

Proportion of patients achieving PASI 90
At Week 52:

Proportion of patients achieving an sPGA (0)
To assess efficacy of 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W as compared to 
secukinumab with respect to clinical response
At Week 52 and at various time points during the 
Maintenance Dosing Period:

Proportion of patients achieving PASI 90

Proportion of patients achieving a DLQI total 
score of (0,1) with at least a 5-point 
improvement (reduction) from baseline in 
patients with a baseline DLQI total score 5

Proportion of patients achieving DLQI (0,1) 
with DLQI baseline score >1
Evaluate the pharmacokinetics and 
pharmacokinetic/pharmacodynamic relationship of 
mirikizumab

Clearance and volume of distribution of 
mirikizumab

Relationship between mirikizumab exposure 
and efficacy (sPGA and PASI)
Abbreviations:  BSA = body surface area; DLQI = Dermatology Life Quality Index; MCS = mental component 
summary; NAPSI = Nail Psoriasis Severity Index;  PASI = Psoriasis Area and Severity Index; 
PASI 75/90/100 = 75%/90%/100% improvement in PASI from baseline; PatGA  = Patient’s Global 
Assessment; PCS = physical component summary ; PPASI = Palmoplantar Psoriasis Severity Index; 
PSS = Psoriasis Symptoms Scale; PSSI = Psoriasis Scalp Severity Index; Q8W = every 8 weeks; 
QIDS-SR16 = 16-item Quick Inventory of Depressive Symptomatology; SF-36 = Short Form 36-item Health 
Survey; sPGA = static Physician’s Global Assessment; WPAI PSO = Work Productivity Activity Impairment 
Questionnaire – Psoriasis.
a
All primary and major secondary endpoint analyses will utilize the multiplicity control technique called 
“graphical multiple testing procedure” to control the overall family-wise Type I error rate.
b
Note: A “clinically meaningful” response is a PASI 75 response, which represents at least a 75% decrease 
(improvement) from the baseline PASI score. A “high level” of clinical response is a PASI 90 response, which 
represents at least a 90% decrease (improvement) from baseline in PASI score, or sPGA (0,1) response, which 
represents an “almost clear” response.  The “highest level” of clinical response is a PASI 100 or sPGA (0) 
response, which represents complete resolution of psoriasis.
Statistical Analysis:
For assessments of the primary and major secondary endpoints and other categorical efficacy and 
health outcome endpoints, the Cochran–Mantel–Haenszel (CMH) chi-square test along with 
Non-Responder Imputation (NRI) will be used to compare the treatment groups.  The CMH 
stratification factors will be the same as those used in the stratified randomization scheme.  The 


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CMH chi-square p-value will be provided.  In addition, the absolute treatment difference in 
proportions will be provided along with the 95% 2-sided confidence interval estimate.
Section 4. Objectives and Endpoints
Table AMAJ.2.
Objectives and Endpoints
Objectives
Endpoints
Primarya,b
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to high levels of 
clinical response
At Week 16:

Proportion of patients with an sPGA (0,1) with 
at least a 2-point improvement from baseline

Proportion of patients achieving a 90% 
improvement in PASI from baseline (PASI 90)
To assess whether mirikizumab induction dosing is 
noninferior to secukinumab with respect to high levels 
of clinical response
At Week 16:

Proportion of patients with an sPGA (0,1) with 
at least a 2-point improvement from baseline

Proportion of patients achieving PASI 90
Major Secondarya,b
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to an early, clinically 
meaningful response
At Week 4:

Proportion of patients achieving a 75% 
improvement in PASI (PASI 75)
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to clinically 
meaningful response and highest levels of 
clinical response
At Week 16:

Proportion of patients achieving a 75% 
improvement in PASI (PASI 75)

Proportion of patients achieving a 100% 
improvement in PASI from baseline (PASI 100)
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to body surface area 
(BSA) affected by psoriasis
At Week 16:

Proportion of patients with ≤1% of BSA with 
psoriasis involvement
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to patient-reported 
outcomes
At Week 16:

Proportion of patients with a PSS symptoms 
score of 0 (free of itch, pain, stinging, and 
burning) in those with a PSS symptoms score 
1 at baseline

Proportion of patients achieving a DLQI total 
score of (0,1) with at least a 5-point 
improvement (reduction) from baseline in 
patients with a baseline DLQI total score 5
To assess whether mirikizumab induction dosing is 
noninferior to secukinumab with respect to high levels 
of clinical response
At Week 16:

Proportion of patients with an sPGA (0,1) with 
at least a 2-point improvement from baseline

Proportion of patients achieving PASI 90


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To assess whether mirikizumab induction dosing is 
noninferior to secukinumab with respect to high levels 
of clinical response
At Week 24:

Proportion of patients achieving PASI 90
To assess whether 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W maintenance dosing is
noninferior to secukinumab with respect to high and 
highest levels of clinical response
At Week 52:

Proportion of patients achieving sPGA (0,1)

Proportion of patients achieving PASI 90

Proportion of patients achieving PASI 100
To assess whether 250 mg mirikizumab maintenance
Q8W and 125 mg mirikizumab Q8W dosing is
superior to secukinumab with respect to high levels 
of clinical response
At Week 52:

Proportion of patients achieving sPGA (0, 1)

Proportion of patients achieving PASI 90

Proportion of patients achieving PASI 100
Other Secondaryb
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to an early, clinically 
meaningful response
To compare mirikizumab to placebo with respect to 
clinical response and time to clinical response during 
the induction dosing period, and with respect to patient-
reported outcomes during the induction dosing period
At Week 4:

Proportion of patients achieving a 75% 
improvement in PASI (PASI 75)
At Week 16 and various time points over the first 
16 weeks of dosing:

Proportion of patients achieving PASI 90

Change from baseline in PPASI total score in 
patients with palmoplantar involvement 
at baseline

Change in PSSI total score in patients with 
scalp involvement at baseline

Change from baseline in NAPSI total score in 
patients with fingernail involvement 
at baseline

Change from baseline on the SF-36 physical 
component summary (PCS) and mental 
component summary (MCS) 

Change from baseline on PatGA of disease 
severity

Change from baseline for the WPAI PSO 
scores (Absenteeism, Presenteeism, Work 
Productivity Loss, and Activity Impairment)

Change from baseline in QIDS-SR16 total 
score in those with a baseline QIDS-SR16 
total score 11

Proportion of patients achieving a DLQI total 
score of (0,1) with at least a 5-point 
improvement (reduction) from baseline in 
patients with a baseline DLQI total score 5

Proportion of patients achieving DLQI (0,1) 
with DLQI baseline score >1


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To compare mirikizumab to secukinumab with respect 
to clinical response and time to clinical response during 
the induction dosing period, and with respect to patient-
reported outcomes during the induction dosing period
At Week 16 and various time points over the first 
16 weeks of dosing:

Proportion of patients achieving PASI 90 
To assess whether 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W maintenance dosing is 
noninferior to secukinumab with respect to high levels 
of clinical response
At Week 24:

Proportion of patients achieving PASI 90
At Week 52:

Proportion of patients achieving an sPGA (0)
To assess efficacy of 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W as compared to 
secukinumab with respect to clinical response
At Week 52 and at various time points during the 
Maintenance Dosing Period:

Proportion of patients achieving PASI 90

Proportion of patients achieving a DLQI total 
score of (0,1) with at least a 5- point 
improvement (reduction) from baseline in 
patients with a baseline DLQI total score 5

Proportion of patients achieving DLQI (0,1) 
with DLQI baseline score >1
Evaluate the pharmacokinetics and 
pharmacokinetic/pharmacodynamic relationship 
of mirikizumab

Clearance and volume of distribution of 
mirikizumab

Relationship between mirikizumab exposure 
and efficacy (sPGA and PASI)
Exploratory
To evaluate the potential development of anti-
mirikizumab antibodies and their potential relationship 
with efficacy, TEAEs, and mirikizumab exposure
At Week 16 and Week 52:

Relationship between TE-ADA and efficacy 
(sPGA and PASI)

Relationship between TE-ADA and TEAEs

Relationship between TE-ADA and 
mirikizumab pharmacokinetics
Abbreviations:  BSA = body surface area; DLQI = Dermatology Life Quality Index; MCS = mental component 
summary; NAPSI = Nail Psoriasis Severity Index;  PASI = Psoriasis Area and Severity Index; 
PASI 75/90/100 = 75%/90%/100% improvement in PASI from baseline; PatGA = patient’s global 
assessment; PCS = physical component summary ; PPASI = Palmoplantar Psoriasis Severity Index; 
PSS = Psoriasis Symptoms Scale; PSSI = Psoriasis Scalp Severity Index; Q8W = every 8 weeks; 
QIDS-SR16 = 16-item Quick Inventory of Depressive Symptomatology; SF-36 = Short Form 36-item Health 
Survey; sPGA = static Physician’s Global Assessment; TE-ADA = treatment-emergent anti-drug antibody;
TEAE = treatment emergent adverse event; WPAI PSO = Work Productivity Activity Impairment 
Questionnaire – Psoriasis.
a
All primary and major secondary endpoint analyses will utilize the multiplicity control technique called 
“graphical multiple testing procedure” to control the overall family-wise Type I error rate.
b
Note: A “clinically meaningful” response is a PASI 75 response, which represents at least a 75% decrease 
(improvement) from the baseline PASI score. A “high level” of clinical response is a PASI 90 response, which 
represents at least a 90% decrease (improvement) from baseline in PASI score, or sPGA (0,1) response, which 
represents an “almost clear” response.  The “highest level” of clinical response is a PASI 100 or sPGA (0) 
response, which represents complete resolution of psoriasis. 


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Section 9.3. Treatment of Overdose
Refer to the Product Label of sekukinumabsecukinumab for advice on overdose.
Section 9.4. Safety
9.4.4. Immunogenicity Assessments
Samples from patients treated with sekukinumabsecukinumab will not be analyzed for anti-
sekukinumabsecukinumab antibodies.  These samples will be discarded at the end of the study.
Section 10.3. Statistical Analyses
10.3.1. General Statistical Considerations
For assessments of the primary endpoints and other categorical efficacy and health outcomes 
endpoints, the Cochran–Mantel–Haenszel (CMH) chi-square test will be used to compare the 
treatment groups with the stratification factors mentioned above.  The CMH chi-square p-value 
will be provided.  In addition, the absolute treatment difference in proportions will be provided 
along with the 95% 2-sided confidence interval estimate.
Treatment comparisons of continuous efficacy and health outcome variables with multiple post-
baseline measurements will be made using mixed-effects model for repeated measures (MMRM) 
analysis.  Sensitivity Secondary analysis on key continuous efficacy and health outcome 
variables will also be performed using analysis of covariance (ANCOVA).  The log-rank test 
will be used to analyze the time to clinical response in the induction period.
10.3.1.1. Missing Data Imputation
Additional missing data imputation methodologies, for example, modified baseline observation 
carried forward (mBOCF), may be considered as sensitivity secondary analyses and will be fully 
detailed in the SAP.  By using mBOCF, for patients discontinuing study treatment due to an AE, 
the baseline observation will be carried forward to the corresponding primary endpoint for 
evaluation.  For patients discontinuing investigational product for any other reason, the last 
nonmissing postbaseline observation before discontinuation will be carried forward to the 
corresponding primary endpoint for evaluation.  
10.3.3. Efficacy Analyses
Non-inferiority Margin and Analyses:
Similarly, a 10% NI margin will be used for the other primary major secondary endpoint sPGA 
(0,1), with noninferiority tests comparing mirikizumab and secukinumab.
There are several major secondary or other secondary endpoints to be tested for NI between each 
mirikizumab dose and secukinumab at Week 24 and Week 52 (Table AMAJ.5).  For ethical 
reasons, patients will need to be crossed over to an active treatment after Week 16 in psoriasis 
studies.  Therefore, no historical data of placebo rates on these endpoints were available, and 
there will be no placebo group beyond Week 16 in Study AMAJ.  Instead, with a reasonable and 
conservative assumption that placebo rates at Week 16 could be carried over to the maintenance 


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period (at both Week 24 and Week 52), the treatment effects between secukinumab and placebo 
at Week 24 and Week 52 on the endpoints are summarized below.  The proposed NI margin of 
10% is shown to provide high retention rate of the secukinumab effect and therefore is 
suggestive of a clinically unimportant difference.
Table AMAJ.5.
Proposed Noninferiority Margin for Various Major Secondary
and Other Secondary Endpoints with Noninferiority Tests in 
Study I6T-MC-AMAJ
Estimated Treatment 
Effects for 
Secukinumaba
Proposed 
Noninferiority Margin
Proportion to Preserve 
Secukinumab Effect
PASI 90 at Week 24
70%
10%
85.7%
PASI 90 at Week 52
65%
10%
84.6%
PASI 100 at Week 52
40%
10%
75%
sPGA (0,1) at Week 52
70%
10%
85.7%
Abbreviations:  PASI = Psoriasis Area and Severity Index; sPGA = static Physician’s Global Assessment.
a
Assuming placebo rates carried from Week 16.
10.3.8. Interim Analyses
To support regulatory submission, an analysis including the primary and major secondary 
endpoints will be conducted after all patients complete Week 52 or discontinue early.  If all 
patients have entered the long-term extension Study I6T-MC-AMAH, or discontinued the study 
early, this analysis is deemed as the final analysis.  Otherwise, this analysis will be an interim 
analysis for the primary outcome; the final analysis will be conducted after all patients have 
entered the long-term extension Study I6T-MC-AMAH, or have completed the follow-up period 
of Study AMAJ, or discontinued the study early.


Leo Document ID = 3a62c9c3-4750-464c-af15-a951a7e7ef39
Approver: 
Approval Date & Time: 30-Sep-2019 18:22:18 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 30-Sep-2019 20:14:20 GMT
Signature meaning: Approved
PPD
PPD

SAP_001.pdf: 
 
I6T-MC-AMAJ Statistical Analysis Plan Version 2 
 
 
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: 25-Nov-2019 
 


I6T-MC-AMAJ Statistical Analysis Plan Version 2
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1.
Statistical Analysis Plan: 
I6T-MC-AMAJ:  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 document is confidential and the information contained 
within it may not be reproduced or otherwise disseminated without the approval of Eli Lilly 
and Company or its subsidiaries.  
Note to Regulatory Authorities:  This document may contain protected personal data 
and/or commercially confidential information exempt from public disclosure.  Eli Lilly and 
Company requests consultation regarding release/redaction prior to any public release.  In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.
Mirikizumab (LY3074828)
Eli Lilly and Company
Indianapolis, Indiana USA 46285
[Protocol I6T-MC-AMAJ]
[Phase 3]
Statistical Analysis Plan Version 1 electronically signed and approved by Lilly:  
28 October 2018
Statistical Analysis Plan Version 2 electronically signed and approved by Lilly on date 
provided below.
Approval Date: 25-Nov-2019 GMT


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2.
Table of Contents
Section
Page
1.
Statistical Analysis Plan:  I6T-MC-AMAJ:  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.
Revision History .................................................................................................................8
4.
Study Objectives...............................................................................................................10
5.
Study Design.....................................................................................................................14
5.1.
Summary of Study Design............................................................................................14
5.1.1.
Screening Period..................................................................................................14
5.1.2.
Baseline and Double-Blinded Induction Period (Week 0 to 
Week 16) .............................................................................................................14
5.1.3.
Blinded Maintenance Period (Week 16 to Week 52 [36 
Weeks]) ...............................................................................................................14
5.1.4.
Posttreatment Follow-Up Period (12 Weeks)........................................................15
5.2.
Determination of Sample Size ......................................................................................17
5.3.
Method of Assignment to Treatment ............................................................................18
6.
A Priori Statistical Methods ..............................................................................................19
6.1.
General Considerations ................................................................................................19
6.1.1.
Patient Populations for Analysis...........................................................................19
6.1.1.1.
Study Time Intervals ......................................................................................21
6.1.1.2.
Definition of Study Baseline...........................................................................22
6.1.2.
Analysis Methods.................................................................................................23
6.2.
Adjustments for Covariates ..........................................................................................24
6.3.
Handling of Dropouts or Missing Data.........................................................................25
6.3.1.
Nonresponder Imputation.....................................................................................25
6.3.2.
Mixed-effects Model for Repeated Measures .......................................................25
6.3.3.
Modified Baseline Observation Carried Forward..................................................25
6.3.4.
Tipping Point Analysis.........................................................................................26
6.3.5.
As Observed ........................................................................................................26
6.4.
Multicenter Studies ......................................................................................................27
6.5.
Multiple Comparisons/Multiplicity...............................................................................27
6.6.
Active-Control Studies Intended to Show Non-inferiority ............................................29
6.7.
Patient Disposition .......................................................................................................29
6.8.
Patient Characteristics ..................................................................................................30


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6.8.1.
Demographics and Baseline Characteristics..........................................................30
6.8.2.
Historical Illnesses and Preexisting Conditions ....................................................33
6.9.
Treatment Compliance .................................................................................................34
6.10. Concomitant Therapy...................................................................................................34
6.11. Efficacy Analyses ........................................................................................................35
6.11.1.
Primary Outcome and Methodology.....................................................................55
6.11.2.
Major Secondary Efficacy Analyses.....................................................................55
6.11.3.
Other Secondary Efficacy Analyses .....................................................................55
6.11.4.
Sensitivity Analyses.............................................................................................55
6.12. Health Outcomes/Quality-of-Life Analyses..................................................................55
6.13. Bioanalytical and Pharmacokinetic/Pharmacodynamic Methods...................................55
6.14. Safety Analyses............................................................................................................55
6.14.1.
Extent of Exposure...............................................................................................56
6.14.2.
Adverse Events ....................................................................................................57
6.14.2.1.
Common Adverse Events ...............................................................................58
6.14.2.2.
Deaths, Other Serious Adverse Events, and Other 
Notable Adverse Events..................................................................................58
6.14.3.
Clinical Laboratory Evaluation.............................................................................58
6.14.4.
Vital Signs and Other Physical Findings...............................................................60
6.14.5.
Electrocardiograms ..............................................................................................60
6.14.6.
Immunogenicity...................................................................................................60
6.14.7.
Special Safety Topics including Adverse Events of Special 
Interest.................................................................................................................60
6.14.7.1.
Hepatic Safety................................................................................................61
6.14.7.2.
Infections, including opportunistic infections and serious 
infections........................................................................................................61
6.14.7.3.
Hypersensitivity..............................................................................................62
6.14.7.4.
Injection Site Reactions (ISR).........................................................................62
6.14.7.5.
Cerebro-Cardiovascular Events.......................................................................62
6.14.7.6.
Malignancies ..................................................................................................63
6.14.7.7.
Suicidal Ideation/Behavior and Depression.....................................................63
6.15. Subgroup Analyses.......................................................................................................63
6.15.1.
Efficacy Subgroup Analyses ................................................................................63
6.15.2.
Safety Subgroup Analyses....................................................................................64
6.16. Analysis for Japan Submission.....................................................................................64
6.17. Analysis for Australian Submission..............................................................................64
6.18. Protocol Deviations......................................................................................................64
6.19. Interim Analyses and Data Monitoring.........................................................................65
6.20. Annual Report Analyses...............................................................................................66


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6.21. Clinical Trial Registry Analyses...................................................................................66
7.
Unblinding Plan................................................................................................................67
8.
References ........................................................................................................................68
9.
Appendices .......................................................................................................................71
App.2.1.
Japan Addendum Design and Objectives..............................................................73
App.2.2.
Japan Addendum General Considerations ............................................................74
App.2.3.
Japan Addendum Efficacy/Health Outcome Analyses ..........................................75
App.2.4.
Japan Addendum Safety Analyses........................................................................77


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Table of Contents
Table
Page
Table AMAJ.4.1.Protocol-Defined Objectives and Endpoints...................................................10
Table AMAJ.6.1.Patient Populations for Analysis ....................................................................20
Table AMAJ.6.2.Treatment Groups and Comparisons for Each Study Period and 
Analysis Population.......................................................................................20
Table AMAJ.6.3.Definition of Study Period Time Intervals......................................................22
Table AMAJ.6.4.Patient Characteristics (and Variables for Subgroup Analysis).......................30
Table AMAJ.6.5.Description and Derivation of Efficacy/Health Outcomes Measures and 
Endpoints ......................................................................................................36
Table AMAJ.6.6.Description of Efficacy/Health Outcomes Analyses.......................................50
Table AMAJ.6.7.Summary Tables Related to Adverse Events..................................................58
Table AMAJ.6.8.Summaries/Displays/Analysis for Clinical Laboratory Evaluations................59


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Table of Contents
Figure
Page
Figure AMAJ.5.1.
Illustration of study design for Clinical Protocol I6T-MC-AMAJ..............16
Figure AMAJ.6.1.
Graphical approach to control type 1 error rate for Study 
I6T-MC-AMAJ. ............................................................................................28


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Table of Contents
Appendix
Page
Appendix 1.
Study Visit Definition for Psoriasis Symptoms Scale (PSS)...........................72
Appendix 2.
Analysis Plan for Japan Addendum................................................................73


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3.
Revision History
Statistical Analysis Plan (SAP) Version 1 was approved prior to any unblinding.  
SAP Version 2 was approved after the unblinding to the external safety Data Monitoring 
Committee (DMC), and prior to the first unblinding to the study team.  The changes made to this 
SAP are as follows:

updated the Study Objectives and Study Design figure per Protocol Amendment 
A and B

updated Table AMAJ.6.2 the treatment group descriptions and Table AMAJ.6.3
the Study Period definition

modified the study baseline definition to be more conclusive

updated the details for common risk difference, categorical mixed-model repeated 
measures (MMRM), tipping point analysis, and as-observed analysis

modified multicenter studies to be subgroup analyses

updated the section of adjustment for covariates

updated the figure of the graphical approach per Protocol Amendment B

updated the prior psoriasis therapy and others in the table of patient characteristics 
and variables for subgroup analysis

included the adverse events (AEs) occurring prior to the first dose for preexisting 
conditions

changed the population for treatment compliance to Induction Safety Population

updated the reporting details of concomitant therapy

updated Table AMAJ.6.5 and Table AMAJ.6.6 with additional details, including:  
o
changed the description of consistent maintenance to be a stability analysis
o
added the details for cumulative time with 90% improvement in Psoriasis 
Area and Severity Index from baseline (PASI 90)
o
revised the analysis for the Patient’s Global Assessment of Psoriasis, and 
facial psoriasis
o
revised Short Form 36-item Health Survey (SF-36) domain score analysis 
with the Responder Definition
o
added analysis to EuroQol 5 Dimensions (EQ-5D) dimension scores
o
added details for 16-item Quick Inventory of Depressive Symptomatology
(QIDS-SR16) domain derivation
o
updated the time point and added the period for table of description of the 
analyses
o
added maintenance of PASI 90/PASI 100 response analysis based on 
responders at Week 16 and Week 24

updated the interpretation of p-values for safety sections

added listing of deaths and clarified some AE reporting by preferred term (PT)
instead of nested within System Organ Class (SOC)

updated the details of hypersensitivity analysis

modified the subgroup analysis


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
added the section of analysis for Japan submission and the Appendix of Analysis 
Plan for the Japan Addendum

added the section of analysis for Australian submission

updated the details of early pharmacokinetics (PK) datalock

updated Appendix 1 to clarify the week/visit mapping

made other minor typographical corrections and clarifications not affecting 
content


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4.
Study Objectives
Table AMAJ.4.1 shows the protocol-defined objectives and endpoints of the study.  In addition, 
the analysis of some non-protocol-defined endpoints is described in Section 6.11 to provided 
supportive evidence of efficacy.  
The estimand (ICH E9 R1) associated with each endpoint/analysis is documented in the 
following places: 

The population of interest is described in the protocol inclusion/exclusion criteria 
and in this document in Table AMAJ.6.1 and Table AMAJ.6.6.

The endpoints/variables are listed in Table AMAJ.4.1, Table AMAJ.6.5, and Table 
AMAJ.6.6.

The handling of intercurrent events is summarized in Section 6.3 and Table 
AMAJ.6.6.

Population summary measures are described in Section 6.10 and Table AMAJ.6.6.
Table AMAJ.4.1.
Protocol-Defined Objectives and Endpoints
Objectives
Endpoints
Primarya,b
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to high levels of 
clinical response
At Week 16:

Proportion of patients with an sPGA (0,1) with 
at least a 2-point improvement from baseline

Proportion of patients achieving a 90% 
improvement in PASI from baseline (PASI 90)
Major Secondarya,b
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to clinically 
meaningful response and highest levels of 
clinical response
At Week 16:

Proportion of patients achieving a 75% 
improvement in PASI (PASI 75)

Proportion of patients achieving a 100% 
improvement in PASI from baseline 
(PASI 100)
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to body surface area 
(BSA) affected by psoriasis
At Week 16:

Proportion of patients with ≤1% of BSA with 
psoriasis involvement
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to patient-reported 
outcomes
At Week 16:

Proportion of patients with a PSS symptoms 
score of 0 (free of itch, pain, stinging, and 
burning) in those with a PSS symptoms score 
1 at baseline

Proportion of patients achieving a DLQI total 
score of (0,1) with at least a 5-point 
improvement (reduction) from baseline in 
patients with a baseline DLQI total score 5


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Protocol-Defined Objectives and Endpoints
Objectives
Endpoints
Major Secondarya,b
To assess whether mirikizumab induction dosing is 
noninferior to secukinumab with respect to high levels 
of clinical response
At Week 16:

Proportion of patients with an sPGA (0,1) with 
at least a 2-point improvement from baseline

Proportion of patients achieving PASI 90
To assess whether 250-mg mirikizumab Q8W and 
125-mg mirikizumab Q8W maintenance dosing is 
noninferior to secukinumab with respect to high and 
highest levels of clinical response
At Week 52:

Proportion of patients achieving sPGA (0,1)

Proportion of patients achieving PASI 90

Proportion of patients achieving PASI 100
To assess whether 250-mg mirikizumab maintenance 
Q8W and 125-mg mirikizumab Q8W dosing is
superior to secukinumab with respect to high levels 
of clinical response*
At Week 52:

Proportion of patients achieving sPGA (0,1)

Proportion of patients achieving PASI 90

Proportion of patients achieving PASI 100
Other Secondaryb
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to an early, clinically 
meaningful response
To compare mirikizumab to placebo with respect to 
clinical response and time to clinical response during 
the induction dosing period, and with respect to 
patient-reported outcomes during the induction 
dosing period
At Week 4:

Proportion of patients achieving PASI 75
At Week 16 and various time points over the first 
16 weeks of dosing:

Proportion of patients achieving PASI 90

Change from baseline in PPASI total score in 
patients with palmoplantar involvement 
at baseline

Change in PSSI total score in patients with 
scalp involvement at baseline

Change from baseline in NAPSI total score in 
patients with fingernail involvement 
at baseline

Change from baseline on the SF-36 physical 
component summary (PCS) and mental 
component summary (MCS) 

Change from baseline on PatGA of disease 
severity**

Change from baseline for the WPAI PSO 
scores (Absenteeism, Presenteeism, Work 
Productivity Loss, and Activity Impairment)

Change from baseline in QIDS-SR16 total 
score in those with a baseline QIDS-SR16 
total score 11

Proportion of patients achieving a DLQI total 
score of (0,1) with at least a 5-point 
improvement (reduction) from baseline in 
patients with a baseline DLQI total score 5

Proportion of patients achieving DLQI (0,1) 
with DLQI baseline score >1


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Protocol-Defined Objectives and Endpoints
Objectives
Endpoints
To compare mirikizumab to secukinumab with respect 
to clinical response and time to clinical response during 
the induction dosing period, and with respect to 
patient-reported outcomes during the induction 
dosing period
At Week 16 and various time points over the first 
16 weeks of dosing:

Proportion of patients achieving PASI 90 
To assess whether 250-mg mirikizumab Q8W and 
125-mg mirikizumab Q8W maintenance dosing is 
noninferior to secukinumab with respect to high levels 
of clinical response
At Week 24:

Proportion of patients achieving PASI 90
At Week 52:

Proportion of patients achieving an sPGA (0)
To assess efficacy of 250-mg mirikizumab Q8W and 
125-mg mirikizumab Q8W as compared to 
secukinumab with respect to clinical response
At Week 52 and at various time points during the 
Maintenance Dosing Period:

Proportion of patients achieving PASI 90

Proportion of patients achieving a DLQI total 
score of (0,1) with at least a 5-point 
improvement (reduction) from baseline in 
patients with a baseline DLQI total score 5

Proportion of patients achieving DLQI (0,1) 
with DLQI baseline score >1
Evaluate the pharmacokinetics and 
pharmacokinetic/pharmacodynamic relationship 
of mirikizumab

Clearance and volume of distribution of 
mirikizumab

Relationship between mirikizumab exposure 
and efficacy (sPGA and PASI)
Exploratory
To evaluate the potential development of 
antimirikizumab antibodies and their potential 
relationship with efficacy, TEAEs, and mirikizumab 
exposure
At Week 16 and Week 52:

Relationship between TE-ADA and efficacy 
(sPGA and PASI)

Relationship between TE-ADA and TEAEs

Relationship between TE-ADA and 
mirikizumab pharmacokinetics


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Protocol-Defined Objectives and Endpoints
Abbreviations:  BSA = body surface area; DLQI = Dermatology Life Quality Index; MCS = mental component 
summary; NAPSI = Nail Psoriasis Severity Index; PASI = Psoriasis Area and Severity Index; 
PASI 75/90/100 = 75%/90%/100% improvement in PASI from baseline; PatGA = Patient’s Global 
Assessment of Psoriasis; PCS = physical component summary; PPASI = Palmoplantar Psoriasis Severity Index; 
PSS = Psoriasis Symptoms Scale; PSSI = Psoriasis Scalp Severity Index; Q8W = every 8 weeks; 
QIDS-SR16 = 16-item Quick Inventory of Depressive Symptomatology; SF-36 = Short Form 36-item Health 
Survey; sPGA = static Physician’s Global Assessment; TE-ADA = treatment-emergent antidrug antibody;
TEAE = treatment-emergent adverse event; WPAI PSO = Work Productivity Activity Impairment 
Questionnaire – Psoriasis.
a
All primary and major secondary endpoint analyses will utilize the multiplicity control technique called 
“graphical multiple testing procedure” to control the overall family-wise Type I error rate.
b
Note: A “clinically meaningful” response is a PASI 75 response, which represents at least a 75% decrease 
(improvement) from the baseline PASI score. A “high level” of clinical response is a PASI 90 response, which 
represents at least a 90% decrease (improvement) from baseline in PASI score, or sPGA (0,1) response, which 
represents an “almost clear” response.  The “highest level” of clinical response is a PASI 100 or sPGA (0) 
response, which represents complete resolution of psoriasis.  
* This objective is written as it is in protocol amendment (b), but should be updated to “To assess whether 250-mg 
mirikizumab maintenance Q8W and 125-mg mirikizumab Q8W dosing is superior to secukinumab with respect 
to high and highest levels of clinical response.” 
** This endpoint is written as it is in protocol amendment (b), but should be updated to “Proportion of patients 
achieving PatGA of disease severity of (0,1) with at least a 2-point improvement from baseline in patients with a 
baseline PatGA ≥2”.


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5.
Study Design
5.1.
Summary of Study Design
Study I6T-MC-AMAJ (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 different mirikizumab doses and regimens, placebo, or secukinumab.  The study is 
comprised of 2 treatment periods (Induction and Maintenance), which together last for up to 
52 weeks, followed by a 12-week Posttreatment Follow-Up Period.
5.1.1. Screening Period  
Screening Period:  Patients will be evaluated for study eligibility ≤28 days before the baseline 
visit (Visit 2).  Electronic diary collection will begin at screening.  
5.1.2. Baseline and Double-Blinded Induction Period (Week 0 to 
Week 16)
At Visit 2 (Week 0; baseline), patients who meet the study eligibility criteria will be randomly 
assigned to their induction and maintenance treatments with stratification based on previous 
exposure to biologic therapy (yes/no), body weight (<100 kg or 100 kg), and geographic region 
(North America, Europe, or Other).  The treatment groups in the Blinded Induction Period are 
250-mg mirikizumab or matching placebo (subcutaneous [SC]) administered at Weeks 0, 4, 8, 
and 12, and 300-mg secukinumab (SC) administered at Weeks 0, 1, 2, 3, 4, 8, and 12.  
Patients who discontinue the study for any reason during this period will stop treatment and 
continue to the early termination visit (ETV) and then complete the 12-week Posttreatment
Follow-Up Period.
5.1.3. Blinded Maintenance Period (Week 16 to Week 52 [36 Weeks])
Patients who were randomly assigned at baseline to receive mirikizumab in the Blinded 
Induction Period were also randomly assigned to receive either 250-mg mirikizumab every 
8 weeks (Q8W) SC or 125-mg mirikizumab Q8W SC in the Blinded Maintenance Period, with 
maintenance dosing starting at Week 16 and ending at Week 48.  Patients who were randomized 
to placebo in the Blinded Induction Period will receive 250-mg mirikizumab SC every 4 weeks 
(Q4W) for Weeks 16 through 32 and 250-mg mirikizumab Q8W thereafter.  Patients who were 
randomized to 300-mg secukinumab SC in the Blinded Induction Period will continue this 
treatment with Q4W dosing during the Blinded Maintenance Period, starting at Week 16 and 
ending at Week 48.
Throughout the study, patients will receive placebo, as appropriate, to maintain the study blind 
across treatment groups.
A discontinuation criterion has been included for patients in any treatment group who remain at 
or above their baseline static Physician’s Global Assessment (sPGA) score at Week 16 (Visit 9) 
and Week 24 (Visit 11), or remain at or above their baseline Psoriasis Area and Severity Index 


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(PASI) score at Week 16 (Visit 9) and Week 24 (Visit 11), to ensure patients who have not 
shown any benefit from study treatment are offered alternative therapies.
At Week 52, patients have 1 of the following options:

Enter Study I6T-MC-AMAH (AMAH), a long-term extension study in which 
patients receive 250-mg mirikizumab Q8W SC or 125-mg mirikizumab Q8W SC, 
OR

Discontinue study treatment and complete Study AMAJ’s 12-week Posttreatment
Follow-Up Period.
Patients who discontinue early from the study for any reason during this period will stop 
treatment and continue to the ETV and then the 12-week Posttreatment Follow-Up Period.
5.1.4. Posttreatment Follow-Up Period (12 Weeks) 
Patients who do not enroll into Study AMAH or who discontinue early from Study AMAJ will 
complete the Posttreatment Follow-Up Period (Visit 801 and Visit 802) of Study AMAJ.
For patients who have entered the Posttreatment Follow-Up Period, psoriasis therapy with 
another agent(s), as determined appropriate by the investigator, is allowed.
Figure AMAJ.5.1 illustrates the study design.  


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Abbreviations:  LV = last study visit; miri = mirikizumab; Q4W = every 4 weeks; 
Q8W = every 8 weeks; SC = subcutaneous; V = visit; w = weeks; W = week.
* Option to enter Study I6T-MC-AMAH or to enter the Posttreatment 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 as shown (patients receiving 125-mg 
miri will receive 1 placebo injection at weeks they receive miri and 2 placebo injections 
at other times shown).  Dosing is via SC injection for all treatments in all periods.
Figure AMAJ.5.1.
Illustration of study design for Clinical Protocol I6T-MC-AMAJ.
Post-Treatment 
Follow-Up Period
W0
V2
W16
V9
W52
V18
LV+4w
V801
LV+12w
V802
Screening
Placebo W0, W1, 
W2, W3, W4, W8, 
W12
Primary Endpoint
250 mg miri W16, W24, 
W32, W40, W48 + 
Placebo W20, W28, 
W36, W44
125 mg miri W16, W24, 
W32, W40, W48 + 
Placebo W16, W20, 
W24, W28, W32, W36, 
W40, W44, W48
300 mg 
secukinumab
W0, W1, W2, W3, 
W4, W8, W12 
Induction
Period
Maintenance
Period
250 mg miri W0, W4, 
W8, W12 + Placebo 
W1, W2, and W3
W 4
V1
*
*
*
*
300 mg secukinumab Q4W
250 mg miri Q4W
at W16 to W32 
250 mg miri Q8W
at W40 and W48
+ Placebo W36, 
W44


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5.2.
Determination of Sample Size
This section is based on the original AMAJ Protocol.  The section was not changed in Protocol 
Amendment (b) due to the completion of the enrollment at the time of Amendment (b) approval.  
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 mirikizumab 
SC Q8W, 250-mg mirikizumab SC at Weeks 0, 4, 8, and 12, then 125-mg mirikizumab SC 
Q8W, 300-mg secukinumab at Weeks 0, 1, 2, 3, and 4, followed by 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).
There are multiple primary endpoints in this study:  the proportion of patients achieving a ≥90% 
improvement in PASI from baseline (PASI 90) and the proportion of patients with a sPGA (0,1) 
with at least a 2-point improvement from baseline, comparisons between mirikizumab and 
placebo (test of superiority), and comparison between mirikizumab and secukinumab (test of 
non-inferiority).  The assumed PASI 90 responses are 70% for the mirikizumab arm, 70% for the 
secukinumab arm, and 3% for the placebo arm.  The assumed sPGA 0 or 1 responses are 70% for 
the mirikizumab arm, 70% for the secukinumab arm, and 5% for the placebo arm.  Both PASI 90 
and sPGA (0,1) rates at Week 52 are estimated to be 75% for both mirikizumab dose groups, and 
65% for secukinumab group.  The assumptions for mirikizumab are based upon the results of the 
mirikizumab Phase 2 Study I6T-MC-AMAF (Reich et al. 2017b) and review of historical clinical 
studies in psoriasis (Langley et al. 2014; Gordon et al. 2016; Blauvelt et al. 2017; Papp et al. 
2017; Reich et al. 2017a).  The assumptions for secukinumab were based upon 2 Phase 3 studies 
of secukinumab for psoriasis (Langley et al. 2014).  
With 888 patients in the mirikizumab group and 111 patients in the placebo group, the estimated 
power is at least 99% to test superiority of mirikizumab to placebo on PASI 90 at Week 16, and 
on sPGA (0,1) at Week 16, respectively, at alpha of 0.05 two-sided.  With 888 patients in the 
mirikizumab group and 444 patients in the secukinumab group, the estimated power is at least 
90% to test noninferiority of mirikizumab to secukinumab at alpha of 0.025 one-sided with a 
noninferiority (NI) margin of 10% on PASI 90 at Week 16.  Similarly, the estimated power is 
least 90% to test noninferiority of mirikizumab to secukinumab at alpha of 0.025 one-sided with 
a NI margin of 10% on sPGA (0,1) at Week 16.
In addition, with 444 patients in the 250-mg mirikizumab Q8W group, 444 patients in 125-mg 
mirikizumab Q8W group, and 444 patients in the secukinumab group, the study will have an 
estimated power of 90% to test superiority of 250-mg mirikizumab Q8W compared to 
secukinumab at alpha of 0.05 two-sided on PASI 90 at Week 52, and sPGA (0,1) at Week 52, 
respectively, as well as 90% power to test superiority of 125-mg mirikizumab Q8W compared to 
secukinumab at alpha of 0.05 two-sided on PASI 90 at Week 52, and sPGA (0,1) at Week 52, 
respectively.  


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5.3.
Method of Assignment to Treatment
Patients who meet all criteria for enrollment will be randomized to double-blind treatment at 
Week 0. Stratified block randomization will be implemented using a computer-generated 
sequence within an interactive web-response system (IWRS).  The randomization will be 
stratified, based on previous exposure to biologic therapy (yes/no), body weight (<100 kg or 
100 kg), and geographic region (North America, Europe, or Other). The IWRS will be used to 
assign prefilled syringes containing double-blind investigational product to each patient.  Site 
personnel will confirm that they have located the correct carton(s) of pre-filled syringes by 
entering a confirmation number found on the carton(s) into the IWRS.


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6.
A Priori Statistical Methods
6.1.
General Considerations
Statistical analysis of this study will be the responsibility of Eli Lilly and Company (Lilly).  The 
latest version of the Medical Dictionary for Regulatory Activities (MedDRA) will be used.
Analyses and summaries from assessment of endpoints described in the protocol (for example, 
described in Table AMAJ.4.1 and in Section 4 of AMAJ protocol) are planned to be included in 
a clinical study report (CSR).  Analyses and summaries for key safety data are also planned to be 
included in the CSR.  Results from additional efficacy analysis pre-defined below and other 
safety analyses may also be provided in the CSR as deemed appropriate.  Any analysis or 
summary not included in the CSR will be available upon request.  
Any change to the data analysis methods described in the protocol will require a protocol 
amendment ONLY if it changes a principal feature of the protocol.  Any other change to the data 
analysis methods described in the protocol and the justification for making the change will be 
described in the CSR.  
Additional exploratory analyses of the data may be conducted as deemed appropriate.  Some of 
these additional supplementary analyses will be prespecified in a separate supplemental SAP.
Some of the analyses described in this document will be incorporated into interactive display 
tools instead of or in addition to static displays.  
The Schedule of Activities outlined in the protocol specifies the allowable windows for 
assessments.  Assessments performed outside these windows will not be excluded from any 
analysis.
6.1.1. Patient Populations for Analysis
Patient populations are defined in Table AMAJ.6.1 along with the analysis they will be used to 
conduct.  Patients will be analyzed according to the treatment to which they were assigned for all 
populations. Table AMAJ.6.2 describes the treatment groups and the comparisons for each study 
period and the analysis population.


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Table AMAJ.6.1.
Patient Populations for Analysis
Population
Description
All Entered Patients
All patients who signed informed consent.  
Intent-to-Treat (ITT)
Population
All randomized patients, even if the patient does not take the assigned treatment, does 
not receive the correct treatment, or otherwise does not follow the protocol.  Unless 
otherwise noted, efficacy and health outcomes analyses for the both induction period and 
combined induction/maintenance periods will be conducted on this population.
Induction Safety
All randomized patients who received at least 1 dose of study treatment.  Safety analyses 
for the induction period will be conducted on this population.
All Active 
Treatment Safety 
All randomized patients who received at least 1 dose of mirikizumab or secukinumab.  
Induction PPS
All randomized patients who do not have important protocol deviations excluded from 
per protocol analysis (IPDPP) in the induction period.  IPDPP are described in a separate 
document referred to as the “The AMAJ Trial Issues Management Plan”.  These patients 
will be used to reanalyze the primary endpoints only.
Induction and
Maintenance PPS
All randomized patients who do not have IPDPP in the combined induction/maintenance 
periods.  IPDPP are described in a separate document referred to as the “The AMAJ Trial 
Issues Management Plan.”  These patients will be used to reanalyze the selected major 
secondary endpoints of PASI 90 and sPGA (0,1) at Week 52.
Abbreviations:  PASI = Psoriasis Area and Severity Index; PASI 90 = ≥90% improvement in PASI from baseline;
PPS = per protocol set; sPGA = static Physician’s Global Assessment.
Table AMAJ.6.2.
Treatment Groups and Comparisons for Each Study Period and 
Analysis Population
Study Period
Analysis 
Population
Treatment Groups
Inferential Comparisons
Induction 
Period
ITT;
Induction Safety;
Induction PPS
placebo Q4W;
300 secu;
250 miri Q4W
300 secu vs placebo Q4W;
250 miri Q4W vs placebo 
Q4W;
250 miri Q4W vs 300 secu
Induction and 
Maintenance 
Periods*
ITT;
Induction and 
Maintenance PPS
placebo/250 miri;
300 secu;
250 miri Q4W/125 miri Q8W;
250 miri Q4W/250 miri Q8W;
Total miri/miri
(Note:  Total miri represents the 
combined treatments of 250 miri 
Q4W/125 miri Q8W and 250 miri 
Q4W/250 miri Q8W.)
250 miri Q4W/125 miri 
Q8W vs 300 secu;
250 miri Q4W/250 miri 
Q8W vs 300 secu
(For efficacy/healthoutcome 
measures, the comparisons 
will be only conducted from 
Week 20 to Week 52)
All Active 
Treatment 
Periods
All Active 
Treatments Safety
placebo/250 miri;
300 secu;
250 miri Q4W/125 miri Q8W;
250 miri Q4W/250 miri Q8W;
all miri
(Note:  all miri represents the combined 
treatments of placebo/250 miri, 250 miri 
Q4W/125 miri Q8W and 250 miri 
Q4W/250 miri Q8W.)
250 miri Q4W/125 miri 
Q8W vs 300 secu;
250 miri Q4W/250 miri 
Q8W vs 300 secu


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Treatment Groups and Comparisons for Each Study Period and Analysis Population 
Study Period 
Analysis 
Population 
Treatment Groups 
 
Inferential Comparisons 
All Active 
Treatment + 
Follow-up 
Periods 
All Active 
Treatment Safety 
 
 
300 secu + FUP; 
all miri + FUP 
(Note:  the header with “+ FUP” is used 
to emphasize that the observations from 
Follow-up Period are included.) 
 
All Periods 
ITT 
 
For study disposition only: 
placebo/250 miri; 
300 secu; 
250 miri Q4W/125 miri Q8W; 
250 miri Q4W/250 miri Q8W; 
Total miri/miri 
 
Induction Safety 
Population 
For hepatic plot only: 
Ever on miri;  
Never on miri 
 
Abbreviations:  FUP = follow-up; ITT = intent-to-treat; miri = mirikizumab; PPS = per protocol set; Q4W = every 4 
weeks; Q8W = every 8 weeks; secu = secukinumab. 
* For some analyses based on response status at certain weeks (Week 16 or 24), only maintenance period will be 
used, and the placebo/250 miri treatment group might not be displayed. 
Note:  for immunogenicity analysis, 300 secu treatment group will be excluded, thus the comparisons involving 
300 secu will not be conducted; also the outputs for the “All Active Treatment Period” and “All Active 
Treatment + Follow-up Periods” will be combined.   
 
6.1.1.1. Study Time Intervals 
Table AMAJ.6.3 displays a list of study periods along with the definition of which patients will 
be considered to have entered the study period and when the individuals start and end the study 
period.  The table shows both a date and a time.   
To calculate the length of any time interval or time period in this study the following formula 
will be used: 
ܮ݁݊݃ݐ݄ ݋݂ ݅݊ݐ݁ݎݒ݈ܽ ሺ݀ܽݕݏሻൌܧ݊݀ ܦܽݐ݁െܫ݊ݐ݁ݎݒ݈ܽ ܵݐܽݎݐ ܦܽݐ݁൅1 
Only for the purpose of calculating the length of study period time intervals, the words “prior to” 
in Table AMAJ.6.3 should be understood to mean “the day before” while the words “after” 
should be understood to mean “the day after.”  
To convert any time length from days to years, the following formula will be used: 
ܮ݁݊݃ݐ݄ ݋݂ ݅݊ݐ݁ݎݒ݈ܽ ሺݕ݁ܽݎݏሻൌܮ݁݊݃ݐ݄ ݋݂ ݅݊ݐ݁ݎݒ݈ܽ ሺ݀ܽݕݏሻ/365.25 
To convert any time length from days to weeks, the following formula will be used: 
ܮ݁݊݃ݐ݄ ݋݂ ݅݊ݐ݁ݎݒ݈ܽ ሺݓ݁݁݇ݏሻൌܮ݁݊݃ݐ݄ ݋݂ ݅݊ݐ݁ݎݒ݈ܽ ሺ݀ܽݕݏሻ/7 


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Table AMAJ.6.3.
Definition of Study Period Time Intervals
Study Period
Start Definition
End Definition
Screening:
All patients who sign informed 
consent are considered as entering 
the Screening Period.
Informed consent date
Prior to the start of induction
Induction Period:
All patients who are randomized to 
the study are considered as entering 
the Induction Period.
At the first injection following 
randomization date/timea.  For patients 
who are randomized but not dosed, the 
Induction Period starts on the date of 
randomization.  
Prior to the start of 
maintenance.  For patients who 
discontinue before or on the 
Week 16 visit, the induction 
period ends at the last date of 
treatment discontinued date or 
last treatment visit date.
Maintenance Period:
All patients who had any Week 16 
to Week 52 visits (except the ones 
who discontinued the study at 
Week 16) are considered to have 
entered the Maintenance Period.  
At the Week 16 dosing date/time.a  If a 
patient is unable to be dosed at the 
Week 16 visit, the Maintenance Period 
starts at the Week 16 visit.  If the 
patient misses the Week 16 visit, the 
Maintenance Period starts at Day 118.
After the Week 52 visit date.  If 
patients discontinued prior to 
Week 52, the Maintenance 
Period ends at the last date of 
treatment discontinued or last 
treatment visit date.  
Induction and Maintenance 
Periods
Use the definition of the start of the 
Induction Period.  
Use the definition of the end of 
Maintenance Period.
Follow-up Period:
All patients who had Visit 801 or 
802 are considered to have entered 
the Follow-up Period.
The latest of the following dates:  
(1) after the end of the Induction Period
as described above, (2) after the end of 
the Maintenance Period as described 
above
The last date of the last study 
visit and study disposition date
All Active Treatment Periods:
All patients who are treated with 
mirikizumab or secukinumab are 
considered to have entered this 
period.
For mirikizumab and secukinumab 
induction treatment groups, use the 
definition of the start of Induction 
Period;
For placebo/250 miri treatment group, 
use the definition of the start of 
Maintenance Period.
The latest of the following 
dates:  (1) the end of the 
Induction Period, (2) the end of 
the Maintenance Period
All Periods (Induction +
Mainteance + Follow-up Periods)
Induction period start date
The last date of the last study 
visit and study disposition date
a
Missing dose time will be imputed as the earliest time that is consistent with available data about dose time.  For 
example, suppose the minutes are missing but hour is present; in this case, we would impute the minutes to be 0.
6.1.1.2.
Definition of Study Baseline
For efficacy and health outcomes, study baseline is defined as the last nonmissing assessment 
(including unscheduled visits) before the first injection, which in most cases will be the 
measurement recorded at Week 0 (Visit 2).  For efficacy/health outcome measures, if the patient 
does not take any injection, the last available value on or prior to randomization date will be 
used.  In cases where baseline measurements are taken on the same day as injection, these 
measurements will be used as the baseline values for data analysis.


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For the Psoriasis Symptoms Scale (PSS), the weekly average of at least 4 days of the consecutive 
7 days prior to the first injection (or randomization, if the patient does not take any injection) will 
be the study baseline score.  
Baseline for safety analysis is described in the safety section.
6.1.2. Analysis Methods
For assessments of the primary endpoints and other binary efficacy and health outcomes 
endpoints, the following will be provided:  

Crude proportions for each treatment group along with the 95% two-sided asymptotic 
(that is, not continuity corrected) confidence intervals (CIs) will be provided.

The estimated common risk difference along with 95% CIs.  The common risk 
difference is the difference in proportions adjusted for the stratification factors as 
mentioned in Section 6.2. SAS® PROC FREQ will be used for the estimates and CIs, 
where the CIs are calculated by using Mantel-Haenszel-Sato method (Sato 1989).

Cochran-Mantel-Haenszel (CMH) test will be used to compare the treatment groups 
while adjusting for the stratification factors as mentioned in Section 6.2.  The CMH 
p-value will be reported, and the CMH adjusted odds ratio along with the 95% 
two-sided asymptotic (that is, not continuity corrected) CIs.
When specified as a sensitivity analysis for binary endpoints, logistic regression with a Firth 
penalized likelihood will be used.  The model will include the treatment groups and the 
covariates described in Section 6.2. Firth correction is equivalent to specifying Jeffrey’s prior 
and seeking the mode of the posterior distribution.  Roughly, it adds half of an observation to the 
data set assuming that the true values of the regression parameters are equal to 0.  The likelihood 
function is adjusted by a fixed quantity, which reduces the positive bias of small samples.  The 
fixed quantity is a function of the information, which goes to 0 as sample size increases.  Firth 
correction can be implemented in PROC Logistic by including ‘firth’ as an option in the model 
statement.  The odds ratio and the corresponding 95% CIs, as well as the treatment differences 
and the corresponding 95% CIs, will be reported.
In addition, when specified as a secondary analysis, pseudo-likelihood-based MMRM
(Categorical MMRM, Agresti 2003) estimating the percentage of patients achieving response 
across postbaseline visits may be used.  When MMRM is used, the model includes treatment, 
baseline value (continuous), visit, the interaction of the baseline value by visit, the interaction of 
treatment by visit, and the induction/maintenance covariates mentioned in Section 6.2 as fixed 
factors.  The binomial distribution and the logit link function will be used.  The residual 
pseudolikelihood with a subject-specific expansion (RSPL) will be used, which is equivalent to
the restricted maximum likelihood (REML).  An unstructured covariance matrix will be used to 
model the within-patient variance-covariance errors.  If the unstructured covariance matrix 
results in a lack of convergence, the heterogeneous Toeplitz covariance structure, followed by 
the heterogeneous autoregressive covariance structure will be used.  The Kenward-Roger 
approximation will be used to estimate the denominator degrees of freedom.  The Newton-
Raphson with ridging optimization technique will be used to aid with convergence.  The 


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probability of response, the corresponding 2-sided 95% CI, and the p-value for the treatment
comparisons at postbaseline visits will be reported.
Treatment comparisons of continuous efficacy and health outcome variables with multiple 
postbaseline measurements will be made using MMRM.  When MMRM is used, the model 
includes treatment, baseline value, visit, the interaction of the baseline value-by-visit, the 
interaction of treatment-by-visit, and the induction/maintenance covariates mentioned in 
Section 6.2 as fixed factors.  The covariance structure to model the within-patient errors will be 
unstructured.  If the unstructured covariance matrix results in a lack of convergence, the 
heterogeneous Toeplitz covariance structure, followed by the heterogeneous autoregressive 
covariance structure will be used.  The REML will be used.  The Kenward-Roger method will be 
used to estimate the denominator degrees of freedom.  Type III tests for the least squares (LS) 
means will be used for the statistical comparison; the 95% CI will also be reported.
Treatment comparisons of continuous efficacy and health outcome variables with a single 
postbaseline time point will be made using analysis of covariance (ANCOVA) with the 
following in the model:  treatment group, baseline value, and Induction Period/Maintenance 
Period covariates mentioned in Section 6.2.  Type III tests for LS means will be used for 
statistical comparison between treatment groups.  The LS mean difference, standard error, 
p-value, and 95% CI, unless otherwise specified, will also be reported.  ANCOVA may also be 
used as a secondary analysis for the MMRM approach, by repeating analysis for each time 
point.  
The Kaplan-Meier (KM) product limit method will be used to estimate the survival for several 
time to event analyses.  The hazard ratio and log-rank test stratified by covariates mentioned in 
Section 6.2 will be reported.  Time for all analyses will be described in units of weeks.  
For variables that are not collected at each postbaseline visit, data may exist at visits where the 
variable was not scheduled to be collected.  In these situations, data from the early 
discontinuation visit that do not correspond to the planned collection schedule will be excluded 
from the MMRM analysis (Andersen and Millen 2013).  Also for by-visit summaries/displays 
such as boxplots, the weeks when data was not scheduled to be collected may not be displayed.  
However, unscheduled assessments within any defined study period will still be used in the shift 
analyses, and for imputing values for the change from baseline to modified baseline observation 
carried forward (mBOCF) endpoint analyses.
6.2.
Adjustments for Covariates
Unless otherwise specified, the statistical analysis models for the efficacy will include 
adjustment for the covariates:  previous exposure to biologic therapy (yes/no), body weight 
(<100 kg or 100 kg), and geographic region (North America, Europe, or Other).  These 
covariates correspond to the stratification factors to be used during randomization.  When 
MMRM or ANCOVA is used, additional covariates, such as baseline will be used as described in 
Section 6.1.2.


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6.3.
Handling of Dropouts or Missing Data
Intercurrent events (ICH E9R1) are events which occur after the treatment initiation and make it 
impossible to measure a variable or influence how it should be interpreted.  Examples of such 
events include treatment discontinuation due to death or AEs, rescue treatment, and loss to 
follow-up.  The missing data methods described below handle intercurrent events in different 
ways.
6.3.1. Nonresponder Imputation
The nonresponder imputation (NRI) method can be justified based on the composite strategy 
(ICH E9R1) for handling intercurrent events.  In this strategy patients are defined as responders
only if they meet the clinical requirements for response at the predefined time AND they remain 
on the assigned study treatment.  Failing either criteria by definition makes them nonresponders.  
Analysis of binary categorical efficacy and health outcome variables will be assessed using an
NRI method.  Patients will be considered nonresponders for the NRI analysis if they do not meet 
the clinical response criteria or have missing clinical response data at the analysis time point.  
Randomized patients without at least 1 postbaseline observation will also be defined as 
nonresponders for the NRI analysis.
6.3.2. Mixed-effects Model for Repeated Measures
The MMRM method will be the analysis method for longitudinal continuous measurements.  It 
can be justified based on the hypothetical strategy (ICH E9R1) for handling intercurrent events.  
In this strategy, the scientific question of interest is to assess the effect of study treatment in a 
hypothetical trial where all patients have complete data and continue to take study treatment 
without dropping out of the study or receiving rescue therapy.  The MMRM method assumes 
missing data can bias results but the bias can be attenuated by modeling random effects using the 
within-subject error correlation structure.  These correlations between the repeated 
measurements provide the platform used to account for the bias from subject dropout.  The 
MMRM model details are provided in Section.  
6.3.3. Modified Baseline Observation Carried Forward
An mBOCF analysis will be performed on continuous efficacy and health outcome endpoints.  
For patients discontinuing investigational product due to an AE, the baseline observation will be 
carried forward to the corresponding primary endpoint for evaluation.  For patients discontinuing 
investigational product for any other reason, the last nonmissing postbaseline observation before 
discontinuation will be carried forward to the corresponding primary endpoint for evaluation.  
For all patients with sporadically missing observations prior to discontinuation, the last 
nonmissing observation before the sporadically missing observation will be carried forward to 
the corresponding visit.  Randomized patients without at least 1 postbaseline observation will not 
be included for evaluation with the exception of patients discontinuing study treatment due to an 
AE.


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The mBOCF can be justified based on the composite strategy (ICH E9R1) for handling 
intercurrent events.  It handles the intercurrent event of discontinuing study drug due to an AE by 
defining the patient as not receiving any benefit from study drug after the event.  That is, the 
patient is defined as reverting back to baseline regardless of any continuing efficacy benefits they 
may have received after the event.  For other intercurrent events (for example, rescue treatment 
and discontinuation due to reasons other than an AE) or sporadic missingness, the while-on-
treatment strategy is applied.  That is, the endpoint is defined as the last observed value at or 
before the visit of interest while the patient was still on study drug.
6.3.4.
Tipping Point Analysis
Tipping point analysis will be conducted as sensitivity analysis for primary endpoints including 
PASI 90 and sPGA (0,1) at Week 16.
Within each analysis, the most extreme case will be considered, in which all missing data for 
patients randomized to mirikizumab will be imputed using the worst possible outcomes and all 
missing data for patients randomized to placebo will be imputed with the best possible outcomes:  

Missing responses in the mirikizumab group will be imputed with a range of response 
probabilities, including probabilities of 0, 0.2, 0.4, 0.6, 0.8, and 1.0..

For missing responses in the placebo group, a range of response probabilities 
(probabilities of 0, 0.2, 0.4, 0.6, 0.8, and 1.0) will be used to impute the missing 
values.  Multiple imputed data sets will be generated for each response probability.
Treatment differences between mirikizumab and placebo will be analyzed for each imputed data 
set using CMH test (Section 6.1.2).  Results across the imputed data sets will be aggregated 
using SAS Proc MIANALYZE in order to compute a p-value or 95% CI for the treatment 
comparisons for the given response probability.  If the probability values do not allow for any 
variation between the multiple imputed datasets (for example, all missing responses in the 
placebo and mirikizumab groups are imputed as responders and nonresponders, respectively), 
then the p-value from the single imputed dataset will be used.
6.3.5. As Observed
Summary based on observed data at each postbaseline visit will be provided for some endpoints.  
Descriptive statistics will be reported without inferential comparisons.  Only data from 
completers at the visit are relevant, and therefore the analysis does not need to deal with missing 
data. This estimand is based on the subset of patients who would complete treatment through the 
visit if assigned to it. Therefore, this estimand is conditional and targets the effect of treatment 
conditional on completion of treatment through the time point of interest. Because the estimand 
is defined for a subpopulation conditional on an intercurrent (postrandomization) event, it is not 
causal. The strategy used in this estimand is the one behind the so-called “observed cases” or 
“completers” analysis ubiquitous in the literature but is not one of the recommended strategies in 
the ICH E9(R1).


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6.4.
Multicenter Studies
This study will be conducted by multiple investigators at multiple sites internationally.  
Typically, a logistic regression with treatment, site, and treatment-by-site may be used to assess 
the consistence of treatment effect in sites.  However, due to a large number of sites in the study, 
this logistic regression model will not likely converge. Instead, the subgroup analysis on the 
country and the region will be evaluated.  The countries will be categorized into geographic 
regions:  Asia (Israel, Japan, Korea); North America (Canada, Puerto Rico, United States);
Australia (Australia); Central America/South America (Argentina); and Europe (Czech Republic, 
Germany, France, Hungary, Italy, Poland, Spain, United Kingdom).  Subgroup analysis details 
are provided in Section 6.15.1.
If the treatment-by-country or treatment-by-region interaction is significant at a 2-sided alpha 
level of 0.1, the nature of this interaction will be inspected as to whether it is quantitative (that is, 
the treatment effect is consistent in direction across all countries or regions but not in size of 
treatment effect) or qualitative (the treatment is beneficial in some but not all countries or 
regions).  If the treatment-by-country or treatment-by-region interaction effect is found to be 
quantitative, results from the primary model will be presented.  If the treatment-by-country or 
treatment-by-region interaction effect is found to be qualitative, further inspection will be used to 
identify in which countries or regions mirikizumab is found to be more beneficial.
6.5.
Multiple Comparisons/Multiplicity
A prespecified graphical multiple testing approach (Bretz et al. 2011, 2009) will be implemented 
to control the overall Type I error rate at two-sided alpha of 0.05 and at one-sided alpha of 0.025 
for non-inferiority tests, for all primary and major secondary endpoints.  More specifically, we 
will calculate multiple testing adjusted p-values using “Algorithm 2” described by Bretz et al. 
(2009), and any hypothesis tests with a multiple testing adjusted p-value of less than 0.05 will be 
considered statistically significant.  This graphical approach is a closed testing procedure; hence, 
it strongly controls the family-wise error rate across all endpoints (Bretz et al. 2011, 2009; Alosh 
et al. 2014).  Each hypothesis is represented as a node in a graph.  Directed arrows between the 
nodes with associated weights represent how alpha is passed from its initial allocation to other 
nodes.  The testing scheme will be fully specified by the graph (including nodes, arrows and 
weights) along with the initial alpha allocation.  Figure AMAJ.6.1 describes the graphical 
scheme, and all of our alpha will be allocated to the sPGA (0,1) Week16 endpoint initially.  The 
testing scheme will be finalized before the first unblinding of efficacy data.


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Abbreviations:  BSA = body surface area; DLQI = Dermatology Life Quality Index; 
H = mirakizumab high dose in maintenance period (250 mg Q8W); ITT = intent-to-
treat; L = mirikizumab low dose in maintenance period (125 mg Q8W); NI = 
noninferiority tests; PASI = Psoriasis Area and Severity Index; PBO = placebo; PSS = 
Psoriasis Symptoms Scale; Q8W = every 8 weeks; secu = secukinumab; sPGA = static 
Physician’s Global Assessment; SUP = superiority tests; W16 = Week 16; W52 = 
Week 52.
Note: Underlined: Primary Endpoints.
Note: PSS Symptoms Free at Week 16 is performed for patients with study baseline 
PSS symptoms score ≥1 in ITT population; DLQI (0,1) and reduction in DLQI ≥5 at 
Week 16 is performed for patients with study baseline DLQI ≥5 in ITT population.
Figure AMAJ.6.1.
Graphical approach to control type 1 error rate for Study 
I6T-MC-AMAJ.
α = 0.05
sPGA 0/1 W16 vs PBO
PASI 90 W16 vs PBO
PASI 75 W16 vs PBO
1
0.9
1
PASI 90 W52 L NI vs secu
PASI 90 W52 L SUP vs secu
sPGA 0/1 W52 L NI vs secu
sPGA 0/1 W52 L SUP vs secu
PASI100 W52 L NI vs secu
PASI100 W52 L SUP vs secu
0.1
PASI 90 W52 H NI vs secu
PASI 90 W52 H SUP vs secu
sPGA 0/1 W52 H NI vs secu
sPGA 0/1 W52 H SUP vs secu
PASI100 W52 H NI vs secu
PASI100 W52 H SUP vs secu
1
1
1
1
1
1
1
1
1
1
1
1
PASI 100 W16 vs PBO
1
BSA ≤1% W16 vs PBO
1
PSS symptoms free W16 vs PBO
1
DLQI 0/1 W16 vs PBO
1
sPGA 0/1 W16 NI vs secu
PASI 90 W16 NI vs secu
1


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6.6.
Active-Control Studies Intended to Show Non-inferiority
There is no universally accepted value for what is considered to be a clinically unimportant 
difference between 2 treatments in sPGA (0,1) or PASI 90 response.  Food and Drug 
Administration (FDA) guidance (2016) states that an appropriate non-inferiority margin should 
be based on both clinical and statistical grounds.
For active control treatment secukinumab, the treatment difference between secukinumab 300-
mg Q4W dosing and placebo on PASI 90 responses at Week 16 in the pivotal Phase 3 studies 
were around 71.5% and 70% in the FIXTURE and ERASURE studies, respectively (Langley et 
al. 2014).  In these study designs, there were no placebo controls beyond Week 12.  As the PASI 
90 rates in placebo patients were very low and few fluctuations were observed in the induction 
phases of these studies, the PASI 90 rates at Week 12 (1.5% and 1.2% in the FIXTURE and 
ERASURE studies, respectively) were extrapolated to Week 16 to provide estimates of treatment 
effect with comparisons to placebo at Week 16.  The estimated treatment differences for 
secukinumab 300 mg Q4W (with placebo) were approximately 70% and 69% in the FIXTURE 
and ERASURE studies.  Due to the consistency of treatment effects in pivotal studies of
secukinumab, a fixed NI margin is proposed for Study AMAJ, instead of being based on the 
synthesis method.  
The NI margin of 10% on PASI 90 response is considered to be sufficiently small to be a 
clinically unimportant difference in outcomes between mirikizumab and secukinumab.  It 
represents clinical judgement about the amount of the active control effect that must be retained.  
Assuming the observed treatment effects for secukinumab and placebo in Study AMAJ is similar 
to what have been observed in historical studies, for example, 70%, the proposed NI margin of 
10% is expected to preserve a substantial fraction (85.7%) of the secukinumab effect.  
Similarly, a 10% NI margin will be used for the other primary endpoint sPGA (0,1) and other 
secondary endpoints with non-inferiority tests comparing mirikizumab and secukinumab.  For 
more details, please refer to Section 10.3.3 in protocol.  
The null hypothesis will be rejected if the lower bound of the one-sided 97.5% CI for the 
difference in proportions of responders on mirikizumab minus secukinumab is greater than the 
pre-specified NI margin (-10%), meaning mirikizumab will be deemed non-inferior to 
secukinumab.  If the lower bound of the CI exceeds 0 (the corresponding p-value will also be 
produced), mirikizumab will be deemed superior to secukinumab.
6.7.
Patient Disposition
Subject flow will be summarized for the number of patient who:  entered, failed screening, were 
randomized to each treatment, completed induction , and completed the maintenance period.  Of 
the treatment completers, the number who enter Study AMAH, complete the posttreatment 
follow up, or discontinue the study will be summarized.


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More specifically, the following summaries will be produced.  The screen failures and reasons
for screen failure will be summarized.  The treatment disposition will be summarized for the 
intent-to-treat (ITT) population, with patients who entered the Maintenance Period (Table 
AMAJ.6.3) to be considered to have completed the Induction Period.  Summaries will be by 
treatment group (Table AMAJ.6.2).  Summaries will also include reasons for discontinuation 
from the study tabulated by treatment group.  The study disposition of all patients who were
randomized (that is, ITT population) will be summarized along with the reasons for 
discontinuation.  The completers will be categorized into those completers who entered Study 
AMAH and those who did not.  
All patients who were randomized (that is, in the ITT population) and discontinued from study 
treatment during any period from the study will be listed, and the timing of discontinuation from
the study will be reported.  If known, a reason for their discontinuation will be given.
Patient allocation by region, country, and center/site will be summarized with number of patients 
who entered the study, number of ITT patients for each treatment group, number of patients 
discontinued from study treatment, and number of patients discontinued from the study.
6.8.
Patient Characteristics
6.8.1. Demographics and Baseline Characteristics
Patient demographic variables and baseline characteristics will be summarized by dose and 
overall for the ITT populations with the baseline values.  The continuous variables will be 
summarized using descriptive statistics and the categorical variables will be summarized using 
frequency counts and percentages.  No inferential analysis for the comparability of baseline 
covariates across treatment groups will be performed.  By-patient listings of basic demographic 
characteristics (that is, Age, Sex, Race, Racial subgroup, Ethnicity, Ethnic subgroup, Country, 
Body, Weight) for the ITT population will be provided.  
Table AMAJ.6.4.
Patient Characteristics (and Variables for Subgroup Analysis)
Variable
Quantitative 
Summary
Categorical Summary
Subgroup Analysisa
Week 16
Week 52
Demographic Characteristics
Ageb
Yes
<65 years, ≥65 years
X
X
<40 years, ≥40 years
X
X
Sex
No
Male, Female
X
X
Age within Sex
No
Male <40 years, Male ≥40 years, 
Female <40 years, Female ≥40 
years
Ethnicity
No
Hispanic/Latino, Non-
Hispanic/Non-Latino
X
X
Race
No
American Indian/Alaska Native, 
Asian, Black/African American, 
Native Hawaiian or other Pacific 
Islander, White, or Multiple
X
X


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Patient Characteristics (and Variables for Subgroup Analysis)
Variable
Quantitative 
Summary
Categorical Summary
Subgroup Analysisa
Week 16
Week 52
Demographic Characteristics
Geographic Region
No
North America (Canada, Puerto 
Rico, United States); Europe
(Czech Republic, Germany, 
France, Hungary, Italy, Poland, 
Spain, United Kingdom); Other
(Argentina, Australia, Israel, 
Japan, Korea)
X
X
No
By Country 
X
X
No
Asia (Israel, Japan, Korea); North 
America (Canada, Puerto Rico, 
United States); Australia
(Australia); Central America/South 
America (Argentina); Europe
(Czech Republic, Germany, 
France, Hungary, Italy, Poland, 
Spain, United Kingdom)
X
X
Height (cm)
Yes
None
Weight (kg)
Yes
<80 kg, ≥80 kg
X
X
<100 kg, ≥100 kg
X
X
BMIc
Yes
Underweight (<18.5 kg/m2), 
Normal (≥18.5 and <25 kg/m2), 
Overweight (≥25 and <30 kg/m2), 
Obese (≥30 and <40 kg/m2), 
Extreme obese (≥40 kg/m2)
X
X
Alcohol use
No
Never, Current, Former
Caffeine use
No
Never, Current, Former
Tobacco use
No
Never, Current, Former
X
X
Prior Psoriasis Therapy
Prior systemic therapyd,e
No
Never used, Ever used 
X
X
Prior biologic therapyd
No
Never used, Ever used
X
X
Number prior biologic
therapies
No
0, 1, 2, >2
X
X
Prior non-biologic systemic 
therapye
No
Never used, Ever used
X
X
Number of prior non-biologic 
systemic therapiese
No
0, 1, 2, >2
Prior conventional systemic 
therapyl
No
Never used, Ever used
X
X
Number of prior conventional 
systemic therapiesl
No
0, 1, 2, >2
Prior anti-TNF alphaf
No
Never used, Ever used
X
X
Prior anti-IL 17g
No
Never used, Ever used
Prior anti-TNF alphaf and/or
Prior anti-IL 17g
No
Anti-IL-17 only, Anti-TNF only, 
Both, Neither
Prior topical therapy
No
Never used, Topical prescription 
therapy only, Topical 
nonprescription therapy only, Both
Prior phototherapy  
No
Never used, Ever used
X
X
Prior systemic therapy or 
phototherapy
No
Never used, Ever used
X
X


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Patient Characteristics (and Variables for Subgroup Analysis)
Variable
Quantitative 
Summary
Categorical Summary
Subgroup Analysisa
Week 16
Week 52
Prior Psoriasis Therapy
Prior nonbiologic systemic 
therapy or phototherapy
No
Never used, Ever used
X
X
Prior biologic inadequate 
response (among those who 
had prior biologic therapy)
No
Yes, No
X
X
Prior biologic loss of 
response (among those who 
had prior biologic therapy)
No
Yes, No
X
X
Prior biologic intolerance 
(among those who had prior 
biologic therapy)
No
Yes, No
X
X
Prior biologic inadequate 
response, loss of response, or 
intolerance (among those 
who had prior biologic 
therapy)
No
Yes, No
X
X
Prior biologic failureh (among 
those who had prior biologic 
therapy)
No
Failed, Not failed
X
X
Prior biologic failureh relative 
to prior biologic exposures
No
Not exposed, Exposed but not 
failed, Exposed and failed
Prior systemic failureh 
(among those who had prior 
systemic therapy)
No
Failed, Not failed
X
X
Prior failure, contraindication 
or intolerance to nonbiologic 
systemic agents or 
phototherapy
No
Yes, No
X
X
Psoriasis Duration and Age at Onset
Duration of psoriasis (years) i
Yes
<15, ≥15
X
X
Duration of diagnosis (years)j
Yes
None
Age at onset (years)k
Yes
<25, ≥25
X
X
Area of Involvement
Baseline facial involvement
No
Yes, No
X
X
Baseline nail involvement
No
Yes, No
X
X
Baseline scalp involvement
No
Yes, No
X
X
Baseline palmoplantar 
involvement
No
Palm involvement only, Sole 
Involvement only, Both, Neither
Yes, No
X
X
Baseline psoriatic Arthritis
No
Yes, No
X
X
Baseline Disease Severity
Baseline PASI score
Yes
<20, ≥20
X
X
<15, ≥15
X
X
Baseline sPGA score
No
Moderate (3), Severe (4), or Very 
severe (5)
X
X
Baseline BSA (%)
Yes
<20%, ≥20%
X
X
Baseline PSSI
Yes
None
Baseline NAPSI
Yes
None
Baseline PPASI
Yes
None


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Patient Characteristics (and Variables for Subgroup Analysis) 
Variable 
Quantitative 
Summary 
Categorical Summary 
Subgroup Analysisa 
Week 16 
Week 52 
Baseline Disease Severity 
Baseline PSS sign scores 
Yes 
0, >0 to <1, ≥1 
 
 
Baseline PSS symptom score 
Yes 
0, >0 to <1, ≥1 
 
 
Baseline PatGA 
No 
 0 (Clear), 1, 2, 3, 4, 5 (Severe) 
 
 
Baseline DLQI total score 
Yes 
 
0 or 1, >1 
 
 
≤10, >10 
 
 
<5, ≥5 
 
 
Baseline SF-36 PCS 
Yes 
None 
 
 
Baseline SF-36 MCS 
Yes 
None 
 
 
Baseline WPAI-PSO 
employment status 
No 
Yes, No 
 
 
Baseline WPAI-PSO score 
Yes 
None 
 
 
Baseline QIDS-SR16 score 
Yes 
 
<11, ≥11 
X 
X 
None (0-5), Mild (6-10), Moderate 
(11-15), Severe (16-20), Very 
severe (21-27) 
 
 
Abbreviations:  BMI = body mass index; BSA = body surface area; DLQI = Dermatology Life Quality Index; 
eCRF = electronic case report form; IL-17 = interleukin 17; MCS = Mental Component Summary; NAPSI = Nail 
Psoriasis Severity Index; PASI = Psoriasis Area and Severity Index; PatGA = Patient’s Global Assessment of 
Psoriasis; PCS = Physical Component Summary; PPASI = Palmoplantar Psoriasis Severity Index; PSS = 
Psoriasis Symptoms Scale; PSSI = Psoriasis Scalp Severity Index; QIDS-SR16 = 16-item Quick Inventory of 
Depressive Symptomatology; SF-36 = Short Form 36-item Health Survey; sPGA = static Physician’s Global 
Assessment; TNF = tumor necrosis factor; WPAI-PSO = Work Productivity Activity Impairment Questionnaire 
– Psoriasis. 
a Subgroup analysis will be used for efficacy endpoints only.  See Section 6.15.1 for more details. 
b Age in years will be calculated as length of the time interval from the imputed date of birth (July 1st in the year of 
birth collected in the eCRF) to the date that the patient was randomized. 
c BMI will be calculated as:  ܤܯܫ ሺ݇݃ / ݉ଶሻൌܹ݄݁݅݃ݐ ሺ݇݃ሻ /ሺܪ݄݁݅݃ݐ ሺ݉ሻሻଶ. 
d Biologic systemic therapies include:  Efalizumab, Ustekinumab, Infliximab, Etanercept, Alefacept, Adalimumab, 
Golimumab, Certolizumab pegol, Secukinumab, Ixekizumab, Brodalumab and other biologic agent.   
e Nonbiologic systemic therapies include:  Cyclosporine, Methotrexate, Corticosteroids, Acitretin, Fumaric acid 
derivatives, Apremilast other systemic agent, and psoralen and ultraviolet A (PUVA).   
f Anti-TNF alpha biologics include:  Infliximab, Etanercept, Adalimumab, Golimumab, and Certolizumab pegol. 
g Anti-IL 17 biologics include:  Secukinumab, Ixekizumab, and Brodalumab. 
h Reasons for discontinuation are loss of response or inadequate response. 
i 
Length of the interval (see Section 6.1.1.1) from the date of psoriasis onset to the date of informed consent.   
j 
Length of the interval (see Section 6.1.1.1) from the date of psoriasis diagnosis to the date of informed consent. 
k Age at diagnosis in years will be calculated as the time interval from the imputed date of birth (July 1st in the year 
of birth collected in the eCRF) to the date of psoriasis diagnosis. 
l 
Conventional systemic therapies include:  Cyclosporine, Methotrexate, Corticosteroids, Acitretin, Fumaric acid 
derivatives, and other systemic agent. 
 
6.8.2. Historical Illnesses and Preexisting Conditions 
Historical illness/condition is defined as the condition/event recorded on the Preexisting 
Conditions and Medical History electronic case report form (eCRF) page or on a Prespecified 
Medical History eCRF page with an end date prior to the date of informed consent.   


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Preexisting condition is defined as the condition/event recorded on the Preexisting Conditions 
and Medical History eCRF page or on a Prespecified Medical History eCRF page with a start 
date prior to the date of informed consent, and no end date (that is, the event is ongoing) or an 
end date on or after the date of informed consent.  In addition, the AEs occurring prior to first 
dose are also included.  Notice if a preexisting condition worsens in severity on or after the date 
of informed consent, it will be recorded as an AE on an Adverse Event eCRF page with the date 
of worsening as the start date.   
The number and percentage of patients with pre-existing conditions will be summarized by 
treatment group using the MedDRA PT nested within SOC.  Also, the number and percentage of 
patients with historical illnesses will be summarized by treatment using MedDRA PT nested 
within SOC.  Summaries will be performed for the ITT populations.   
The number and percentage of patients with prespecified medical history (Hypertension, 
Diabetes Type 1, Insulin-requiring Type II Diabetes Mellitus, Diabetes Mellitus Type II 
Noninsulin Dependent, Coronary Artery Disease, Stroke, Dyslipidemia, Psoriatic Arthritis, 
Ulcerative Colitis, Crohn's Disease) by treatment and overall for the ITT Populations. 
6.9. Treatment Compliance 
Treatment compliance with investigational product will be summarized for patients who have at 
least one dose (that is, Induction Safety Population) for the Induction Period and for the 
combined Inducation and Maintenance Periods.  Treatment compliance for each subject will be 
calculated as: 
ܶݎ݁ܽݐ݉݁݊ݐ ܿ݋݉݌݈݅ܽ݊ܿ݁ ሺ%ሻൌ100 ൈܶ݋ݐ݈ܽ ݊ݑܾ݉݁ݎ ݋݂ ݆݅݊݁ܿݐ݅݋݊ݏ ܽ݀݉݅݊݅ݏݐ݁ݎ݁݀
ܶ݋ݐ݈ܽ ݊ݑܾ݉݁ݎ ݋݂ ݆݅݊݁ܿݐ݅݋݊ݏ ݌ݎ݁ݏܿݎܾ݅݁݀ 
 The number of injections prescribed can be derived from the IWRS study drug 
dispense dataset.   
 The total number of injections administered will be derived using the response 
to the question “Was dose administered?” on the Exposure eCRF page. 
A subject will be considered significantly noncompliant if he or she fails to attend for 
administration of study medication within the required treatment window as defined in the 
protocol schedule of activities.  Overall compliance with therapy is defined to be missing no 
more than 20% of the expected doses and not missing 2 consecutive doses.  Proportions of 
patients who demonstrate overall compliance will be compared between treatment groups using 
Fisher’s exact test. 
6.10. Concomitant Therapy 
Medications will be classified into anatomical therapeutic chemical (ATC) drug classes using the 
latest version of the World Health Organization (WHO) drug dictionary.  Medication start and 
stop dates will be compared to the date of first dose of treatment in each treatment period to 
allow medications to be classified as Concomitant for each treatment period.   


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Prior medications are those medications that start and stop prior to the date of first dose of study 
treatment.  Concomitant medications are those medications that start before, on, or after the first 
day of study treatment of the defined treatment period and continue into the treatment period.  
Concomitant medications are assigned to the treatment period in which they are actually 
ongoing.  For example, if a patient is receiving concomitant medication during the Induction 
Period but has a stop date during the Induction Period, the same medication would not be listed 
as a concomitant medication during the latter periods unless patient has a new start date.
For the ITT population, prior therapy (reported before randomization) and current concomitant 
therapy (use during the Induction Period, and combined Induction and Maitenance Periods) will 
be presented separately in frequency tables.  For all summary tables of concomitant medications,
preferred names of concomitant medication will be sorted by descending frequency.
The medical monitor for this study will identify the corticosteroids used by the patients from the 
list of concomitant medication collected during the course of this study.  A summary table for the 
number and percent of patients using corticosteroids during the Induction and combined 
Induction and Maintenance Periods using the ITT population will be presented by the treatment 
groups.  This will include:  (1) topical therapy, (2) topical steroid therapy and (3) systemic 
corticosteroid therapy.  Definition of these 3 classes of interest will be based on compound level
safety standards.  
6.11. Efficacy Analyses
Table AMAJ.6.5 includes the description and derivation of the efficacy/health outcomes 
measures and endpoints.
Table AMAJ.6.6 provides the detailed analyses including analysis type, method and imputation, 
population, time point, and treatment comparisons for efficacy/health outcomes analyses.


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Table AMAJ.6.5. 
Description and Derivation of Efficacy/Health Outcomes Measures and Endpoints 
Measure 
Description 
Variable 
Derivation/Comment 
Imputation Approach if with 
Missing Components 
PASI 
Psoriasis Area and Severity Index (PASI):  
combines assessments of the extent of 
body surface involvement in 4 anatomical 
regions (head and neck, trunk, arms, and 
legs) and the severity of scaling (S), 
redness (R), and plaque 
induration/infiltration (thickness, T) in 
each region, yielding an overall score of 0 
for no psoriasis to 72 for the most severe 
disease (Fredriksson and Pettersson 1978).  
Severity is rated for each index (R, S, T) 
on a 0-4 scale (0 for no involvement up to 
4 for very severe involvement): 
0 = none 
1 = slight 
2 = moderate 
3 = severe 
4 = very severe 
The body is divided into 4 anatomical 
regions comprising the head (h), upper 
limb (u), trunk (t), and lower limb (l).  In 
each of these areas, the fraction of total 
body surface area affected is graded on a 
0-6 scale (0 for no involvement; up to 6 for 
90% - 100% involvement):   
0 = 0% (clear) 
1 = >0% to <10% 
2 = 10% to <30% 
3 = 30% to <50% 
4 = 50% to <70% 
5 = 70% to <90% 
PASI score 
The composite PASI score is calculated by 
multiplying the sum of the individual severity 
scores for each area by the weighted area-of-
involvement score for that respective area, and 
then summing the 4 resulting quantities as 
follows:  
PASI = 0.1(Rh + Th + Sh)Ah + 0.2(Ru + Tu + 
Su)Au + 0.3(Rt + Tt + St)At + 0.4(Rl + Tl + Sl)Al 
Where, 
Rh, Ru, Rt, Rl = redness score of plaques on 
the head, upper limb, trunk, and lower limb, 
scored 0-4 respectively; 
Th, Tu, Tt, Tl = thickness score of plaques on 
the head, upper limb, trunk, and lower limb, 
scored 0-4 respectively; 
Sh, Su, St, Sl = scaliness score of plaques on 
the head, upper limb, trunk, and lower limb, 
scored 0-4 respectively;  
Ah, Au, At, Al = numerical value translation 
of % area of psoriatic involvement score for 
the head, upper limb, trunk, and lower limb, 
respectively. 
PASI scores are treated as a continuous score, 
with 0.1 increments within these values.   
If any individual score is 
missing, the PASI score will 
not be calculated, hence 
missing 
PASI change 
from baseline 
Calculated as:  observed PASI – baseline PASI 
Missing if baseline or 
observed value is missing 
PASI percent 
improvement 
from baseline 
Calculated as: 
ܲ݁ݎܿ݁݊ݐ݅݉݌ݎ݋ݒ݁݉݁݊ݐ ݂ݎ݋ܾ݉ܽݏ݈݁݅݊݁ൌ 
100 ൈܤܽݏ݈݁݅݊݁ ܲܣܵܫെܱܾݏ݁ݎݒ݁݀ ܲܣܵܫ
ܤܽݏ݈݁݅݊݁ ܲܣܵܫ
 
If a patient has experienced an improvement, this 
measure will be positive.  If a patient has 
Missing if baseline or 
observed value is missing 


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6 = 90% to 100% 
The various body regions are weighted to 
reflect their respective proportion of body 
surface area.   
experienced a worsening in the condition, this 
measure will be negative.   
PASI 75 
A clinically meaningful response; at least a 75% 
improvement in PASI score from baseline 
Missing if baseline or 
observed value is missing 
PASI 90 
(Primary) 
Higher level of clearance; at least a 90% 
improvement in PASI score from baseline 
Missing if baseline or 
observed value is missing 
PASI 100 
Complete resolution of plaque Ps; a 100% 
improvement in PASI score from baseline 
Missing if baseline or 
observed value is missing 
Stability of 
PASI 
90/PASI 100 
from Week 
16 to each 
visit up to 
Week 52 
 
Patient has PASI 90/PASI 100 starting from 
Week 16 to (and including all between scheduled 
visits if any) each visit up to Week 52. 
Missing if PASI 90/PASI 100 
is missing for any of Week 16 
to each visit up to Week 52.  
Also missing when patient 
discontinued study treatment 
at or before the analysis visit 
Cumulative 
time with 
PASI 90 
response 
from Week 
16 to Week 
52 
Area under the curve (AUC) of PASI 90 response 
over time among PASI 90 responder starting 
from Week16, using trapezoidal rule (i.e., 100% 
when patients are PASI 90 responders at the visit 
and 0% when patients are non PASI 90 
responders at the visit) 
 
Percentages of scheduled visits with PASI 90 
response among all scheduled visits from Week 
16 to Week 52  
 
Percentages of weeks with PASI 90 response 
from Week 16 to Week 52 
NRI if the observed value is 
missing 
Cumulative 
time with 
PASI 90 
response 
Area under the curve (AUC) of PASI 90 response 
over time among PASI90 responder starting from 
Week 0, using trapezoidal rule (i.e., 100% when 
patients are PASI 90 responders at the visit and 
NRI if the observed value is 
missing 


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from Week 0 
to Week 52 
0% when patients are non-PASI 90 responders at 
the visit) 
 
Percentages of scheduled visits with PASI 90 
response among all scheduled visits from Week 0 
to Week 52 
 
Percentages of weeks with PASI 90 response 
from Week 0 to Week 52 
Time to first 
achieving 
PASI 100, 
PASI 90, or 
PASI 75 (i.e., 
3 different 
analyses) 
during 
Induction 
Period 
For patients who are observed to meet the 
response criteria during the Induction Period, 
time will be from the start of the Induction Period 
to the first measurement date where the patient 
met the response criteria. 
 
Patients not observed to meet 
response criteria during the 
Induction Period will be 
censored after the date of their 
last measurement during the 
Induction Period.  
sPGA 
sPGA:  the physician’s global assessment 
of the patient’s psoriasis lesions at a given 
time point (European Medicines Agency 
[EMA] 2004).  Plaques are assessed for 
induration, erythema, and scaling, and an 
overall rating of psoriasis severity is given 
using the anchors of clear (0), minimal (1), 
mild (2), moderate (3), severe (4), or very 
severe (5). 
sPGA score 
Range from 0-5:  clear (0), minimal (1), mild (2), 
moderate (3), severe (4), or very severe (5) 
Single item, missing if 
missing 
sPGA (0,1)   
(Primary) 
 
An sPGA assessed as either 0 or 1, which 
represents a clinically meaningful response of 
minimal plaque severity or complete resolution of 
plaque psoriasis 
Missing if sPGA is missing 
sPGA (0) 
An sPGA assessed as 0, which represents a 
clinically important endpoint indicating complete 
resolution of plaque psoriasis 
Missing if sPGA is missing 
Time to first 
achieving 
sPGA (0,1) 
during 
Induction 
For patients who are observed to meet the 
response criteria during the Induction Period, 
time will be from the start of the Induction Period 
to the first measurement date where the patient 
met the response criteria. 
Patients not observed to meet 
response criteria during the 
Induction Period will be 
censored after the date of their 
last measurement during the 


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Imputation Approach if with 
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Period 
Induction Period. 
BSA 
 
Percentage of Body Surface Area (BSA): 
The investigator will evaluate the 
percentage involvement of psoriasis on 
each patient’s BSA on a continuous scale 
from 0% (no involvement) to 100% (full 
involvement), in which 1% corresponds to 
the size of the patient’s hand (including the 
palm, fingers, and thumb).   
BSA 
Collected as a single scale as part of PASI 
electronic case report form eCOA.  Range from 
0% to 100%. 
Single item, missing if 
missing 
BSA ≤1% 
BSA assessed as ≤1% with psoriasis involvement 
Missing if BSA is missing 
BSA change 
from baseline 
Calculated as:  observed BSA – baseline BSA  
Missing if baseline or 
observed value is missing 
PSS 
The Psoriasis Symptoms Scale (PSS) is a 
patient-administered assessment of 8 
symptoms:  itch, pain, discomfort, 
stinging, burning, redness, scaling, and 
cracking.  Respondents are asked to 
answer the questions based on their 
psoriasis symptoms.   
 
The overall severity for each individual 
symptom from patient’s psoriasis is 
indicated by selecting the number from an 
NRS of 0-10 that best describes the worst 
level of each symptom in the area in the 
past 24 hours, where 0 (no severity) and 10 
(worst imaginable severity). 
 
The symptom severity scores, ranging 
from 0-10, are the values of the selected 
PSS item 
scores 
The PSS score for each item as reported in daily 
diaries from Visit 1 up to Visit 7.  For each week 
up to Visit 7, a mean score will be calculated.  
See Appendix 1 for details on the study period 
associated with each week and calculation details.  
The PSS will be collected only during office 
visits for the remaining visits.   
For daily diary assessments, at 
least 4 (out of up to 7) 
assessments must be averaged.  
Otherwise, the item is missing.  
For office based assessments, 
the item is missing if it is not 
present in the data. 
PSS 
Symptoms 
Score  
Calculated by summing the individual item scores 
as follows:  itch NRS + pain NRS + stinging NRS 
+ burning NRS 
If any of the 4 relevant item 
score are missing, the score is 
missing 
PSS Signs 
Score 
Calculated by summing the individual item scores 
as follows:  redness NRS + scaling NRS + 
cracking NRS 
If any of the 3 relevant item 
score are missing, the score is 
missing 
PSS 
Symptoms 
Score of 0
Free of itch, pain, stinging, and burning 
Missing if PSS Symptoms 
Score is missing  
PSS Signs 
Score of 0 
Free of redness, scaling, and cracking 
Missing if PSS Signs Score is 
missing  


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numbers indicated by the patient on the 
instrument’s horizontal scale.  Each of the 
8 individual items will receive a score of 
0-10 and will be reported as item scores 
for itch, pain, discomfort, stinging, 
burning, redness, scaling, and cracking.  In 
addition, a total score ranging from 0 (no 
psoriasis symptoms) to 80 (worst 
imaginable psoriasis symptoms) will be 
reported. 
PSS (Signs, 
Symptoms, 
items) Score 
change from 
baseline 
Change from baseline = Observed PSS Score – 
Baseline PSS Score 
Here “PSS Score” could refer to the Total, Signs 
Symptoms, or an item score.  Negative change 
indicates improvement and a positive change 
indicates deterioration of the condition.   
Missing if either observed or 
baseline PSS score is missing  
PSSI 
Psoriasis Scalp Severity Index (PSSI):  
will be used if the patient has scalp 
psoriasis at baseline.  The scalp will be 
assessed for erythema (redness), induration 
(hardness), and desquamation (shedding of 
skin) and percentage of area affected as 
follows:  
Erythema, Induration and Desquamation: 
0 = Absent 
1 = Slight 
2 = Moderate 
3 = Severe 
4 = Severest Possible 
Percent of Scalp Involved: 
0 = none 
1 = <10% 
2 = 10 – 29% 
3 = 30 – 49% 
4 = 50 – 69% 
5 = 70 – 89% 
6 = 90 – 100% 
PSSI score 
The PSSI score is a composite score derived from 
the sum of the scores for erythema, induration 
and desquamation multiplied by the score for the 
extent of scalp area involved (percent of scalp 
involved).  The range is 0-72. 
If any individual score is 
missing, the PSSI score will 
not be calculated, hence 
missing. 
PSSI score 
change from 
baseline 
Calculated as:  observed PSSI – baseline PSSI 
Missing if baseline or 
observed value is missing 
PSSI 
score = 0 
A PSSI response is defined as a PSSI score of 0, 
which is also referred to as scalp clearance. 
Missing if PSSI score is 
missing 


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NAPSI 
 
Nail Psoriasis Severity Index (NAPSI):  in 
patient with baseline fingernail psoriasis 
involvement, NAPSI will be used to 
evaluate the severity of fingernail bed 
psoriasis and fingernail matrix psoriasis by 
area of involvement in the fingernail unit.  
The fingernail is divided with imaginary 
horizontal and longitudinal lines into 
quadrants.  Each fingernail is given a score 
for fingernail bed psoriasis (0-4) and 
fingernail matrix psoriasis (0-4), 
depending on the presence (score of 1) or 
absence (score of 0) of any of the features 
of fingernail bed and fingernail matrix 
psoriasis in each quadrant:   
0 = none 
1 = present in 1 quadrant of nail 
2 = present in 2 quadrants of nail 
3 = present in 3 quadrants of nail 
4 = present in 4 quadrants of nail 
NAPSI score 
change from 
baseline 
The NAPSI score of a fingernail is the sum of 
scores in fingernail bed and fingernail matrix 
from each quadrant (maximum of 8).  Each 
fingernail is evaluated, and the sum of all the 
fingernails is the total NAPSI score (range, 0-80), 
usually indicated as NAPSI score. 
 
For each fingernail, if either 
bed or matrix score is missing 
or not done, the score for that 
finger is missing.  If <50% of 
the finger scores from 10 
fingers are missing, the 
imputation will be performed 
by using the average score of 
the remaining fingernails.  If 
≥50% of the finger scores are 
missing, the NAPSI score will 
be left as missing.   
NAPSI 
score = 0 
Calculated as: observed NAPSI – baseline NAPSI 
Missing if baseline or 
observed value is missing 
NAPSI 
score = 0 
A NAPSI response is defined as a NAPSI score 
of 0, which is also referred to as nail clearance. 
Missing if NAPSI score is 
missing 


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Imputation Approach if with 
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PPASI 
Palmoplantar Psoriasis Area and Severity 
Index (PPASI):  will be used if the patient 
has palmoplantar psoriasis at baseline.  
Both palms and soles on each hand and 
foot will be individually assessed for 
erythema, induration, desquamation and 
percentage of area affected as follows:   
Erythema (E), Induration (I) and 
Desquamation (D): 
0 = None 
1 = Slight 
2 = Moderate 
3 = Severe 
4 = Very Severe 
Percent of Palm and Sole Area Covered: 
0 = None 
1 = <10% 
2 = 10 – 29% 
3 = 30 – 49% 
4 = 50 – 69% 
5 = 70 – 89% 
6 = 90 – 100% 
PPASI score 
The PPASI score is a composite score derived 
from the sum scores for E, I, and D multiplied by 
a score for the extent of palm and sole area 
involvement.  The range is 0-72.   
PPASI = 0.2(Erp +Irp +Drp)Arp + 0.2(Elp 
+Ilp+Dlp)Alp + 0.3(Ers +Irs+Drs)Ars + 0.3(Els 
+Ils+Dls)Als 
Where, 
Erp, Elp, Ers, Els = Erythema score of plaques 
on the right palm (rp), left palm (lp), right 
sole (rs), left sole (ls), scored 0-4 
respectively; 
Irp, Ilp, Irs, Ils = Induration score of plaques on 
the right palm (rp), left palm (lp), right sole 
(rs), left sole (ls), scored 0-4 respectively; 
Drp, Dlp, Drs, Dls = Desquamation score of 
plaques on the right palm (rp), left palm 
(lp), right sole (rs), left sole (ls), scored 0-4 
respectively;  
Arp, Alp, Ars, Als = numerical value translation of 
% area covered for the right palm, left palm, right 
sole, and left sole, respectively. 
If any individual score is 
missing, the PPASI score will 
not be calculated, hence 
missing. 
 
PPASI 
change from 
baseline 
Calculated as:  observed PPASI – baseline PPASI 
Missing if baseline or 
observed value is missing 
PPASI 
percent 
improvement 
from baseline 
Calculated as:   
 
If a patient has experienced an improvement, this 
measure will be positive.  If a patient has 
experienced a worsening in the condition, this 
measure will be negative.   
Missing if baseline or 
observed value is missing 
PPASI 50 
At least a 50% improvement in PPASI score from 
baseline 
Missing if baseline or 
observed value is missing 
ܲ݁ݎܿ݁݊ݐ݅݉݌ݎ݋ݒ݁݉݁݊ݐ ݂ݎ݋ܾ݉ܽݏ݈݁݅݊݁ൌ
100 ൈ
ܤܽݏ݈݁݅݊݁ܲܲܣܵܫെܱܾݏ݁ݎݒ݁݀ܲܲܣܵܫ
ܤܽݏ݈݁݅݊݁ ܲܲܣܵܫ
   


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Variable 
Derivation/Comment 
Imputation Approach if with 
Missing Components 
PPASI 75 
at least a 75% improvement in PPASI score from 
baseline 
Missing if baseline or 
observed value is missing 
PPASI 100 
a 100% improvement in PPASI score from 
baseline 
Missing if baseline or 
observed value is missing 
DLQI 
Dermatology Life Quality Index (DLQI):  
is a validated, dermatology-specific, 
patient-reported measure that evaluates 
patient’s health-related QoL.  This 
questionnaire has 10 items that are 
grouped in 6 domains, including symptoms 
and feelings, daily activities, leisure, work 
and school, personal relationships, and 
treatment.  The recall period of this scale is 
over the “last week”.  Response categories 
and corresponding scores are: 
Very much = 3 
A lot = 2 
A little = 1 
Not at all = 0 
Not relevant = 0 
DLQI total 
score 
A DLQI total score is calculated by summing all 
10 question responses, and has a range of 0-30 
(less to more impairment) (Finlay and Khan 
1994; Basra et al. 2008).   
If 2 or more questions are 
missing, the total score is 
missing.  Note:  #7B could be 
a valid missing while #7A is 
not “No.”  That is, #7 should 
be considered as 1 question. 
DLQI (0,1) 
 
A DLQI (0,1) response is defined as a 
postbaseline DLQI total score of 0 or 1.  A DLQI 
total score of 0 to 1 is considered as having no 
effect on a patient’s HRQoL (Khilji et al. 2002; 
Hongbo et al. 2005). 
Missing if DLQI total score is 
missing 
DLQI total 
score ≥5 
improvement 
from baseline 
Reduction/decrease of ≥ 5 points from baseline.  
A 5-point change from baseline is considered as 
the minimal clinically important difference 
threshold. 
Missing if baseline or 
observed value is missing 
DLQI (0,1) 
and DLQI 
total score ≥5 
improvement 
from baseline 
Patient is a DLQI (0,1) responder and 
reduction/decrease of ≥5 points from baseline.  
Missing if baseline or the total 
score is missing 
DLQI total 
score and 
domain 
scores change 
from baseline 
Calculated as:  observed DLQI (total score or 
domain scores) – baseline DLQI (total score or 
domain scores) 
Missing if baseline or 
observed value is missing 
DLQI 
symptoms 
and feelings 
Sum of responses of questions #1 and #2: 
#1.  How itchy, sore, painful or stinging has your 
skin been? 
If 1 question in a domain is 
missing, that domain is 
missing. 


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domain 
#2.  How embarrassed or self-conscious have you 
been because of your skin? 
DLQI daily 
activities 
domain 
Sum of responses of questions #3 and #4: 
#3.  How much has your skin interfered with you 
going shopping or looking after your home or 
garden? 
#4.  How much has your skin influenced the 
clothes you wear? 
If 1 question in a domain is 
missing, that domain is 
missing. 
DLQI leisure 
domain  
Sum of responses of questions #5 and #6: 
#5.  How much has your skin affected any social 
or leisure activities? 
#6.  How much has your skin make it difficult for 
you to do any sport? 
If 1 question in a domain is 
missing, that domain is 
missing. 
DLQI work 
and school 
domain 
Sum of responses of questions question #7A and 
#7B: 
#7A.  Has your skin prevented you from working 
or studying? 
#7B.  If No:  how much has your skin been a 
problem at work or studying? 
If the answer to question #7A 
is missing, this domain is 
missing.  If #7A is No, and 
#7B is missing, this domain is 
missing. 
DLQI 
personal 
relationships 
domain 
Sum of responses of questions #8 and #9: 
#8.  How much has your skin created problems 
with your partner or any of your close friends 
or relatives? 
#9.  How much has your skin caused any sexual 
difficulties? 
If 1 question in a domain is 
missing, that domain is 
missing. 
DLQI 
treatment 
domain 
Response of question #10: 
#10.  How much of a problem has the treatment 
for your skin been, for example by making 
your home messy, or by taking up time? 
If 1 question in a domain is 
missing, that domain is 
missing. 
WPAI-
PSO 
The Work Productivity and Activity 
Impairment-Psoriasis (WPAI-PSO) 
Questionnaire is a patient-reported 
instrument developed to measure the 
Employment 
Status 
Yes/No 
Missing if question is missing 
Absenteeism 
Score (%) 
ܳ2
ሺܳ2 ൅ܳ4ሻൈ100 
Missing if Q2 or Q4 are 
missing.  Also missing if 


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Derivation/Comment 
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impact on work productivity and regular 
activities attributable to a specific health 
problem (psoriasis).  It contains 6 items 
that measure:  1) employment for pay 
status, 2) hours missed from work due to 
the psoriasis, 3) hours missed from work 
for other reasons, 4) hours actually 
worked, 5) degree of health-affected 
productivity while working, and 6) degree 
of health affected productivity in regular 
unpaid activities. 
Greater scores indicate greater impairment 
(Reilly Associates Health Outcomes 
Research [WWW]). 
Employment Status is No. 
Presenteeism 
Score (%) 
ܳ5
10 ൈ100 
Missing if Q5 is missing.  
Also missing if Employment 
Status is No. 
Work 
Productivity 
Loss Score 
(%) 
൤
ܳ2
ܳ2 ൅ܳ4 ൅൬1 െ
ܳ2
ܳ2 ൅ܳ4൰ܳ5
10൨ൈ100 
Missing if Q2, Q4, or Q5 is 
missing.  Also missing if 
Employment Status is No. 
Activity 
Impairment 
Score (%) 
ܳ6
10 ൈ100 
Missing if Q6 is missing.  
May still be present and 
nonmissing if patient is 
unemployed. 
SF-36 
The SF-36 Version 2 is a 36-item, patient-
completed measure designed to be a short, 
multipurpose assessment of health (The SF 
Community – SF-36 Health Survey 
Update).  The summary scores range from 
0-100, with higher scores indicating better 
levels of function and/or better health.  
Items are answered on Likert scales of 
varying lengths.  The SF-36 comprises 8 
domain scores and 2 overarching 
component scores.  SF-36 domain scores 
are:  (1) Physical functioning, (2) Role-
physical, (3) Role-emotional,  (4) bodily 
pain, (5) vitality, (6) social functioning, (7) 
mental health, and (8) general health.  The 
component scores are:  (1) the Physical 
Component Summary (PCS) and (2) 
Mental Component Summary (MCS). 
 
SF-36 
Domain 
scores and 
SF-36 
Component 
Scores 
Per copyright owner, the Quality Metric Health 
Outcomes™ Scoring Software will be used to 
derive SF-36 domain and component scores. 
 
After data quality-controls, the SF-36 software 
will recalibrate the item-level responses for 
calculation of the domain and component scores.  
These raw scores will be transformed into the 
domain scores (t-scores) using the 1-week recall 
period.  This entails exporting the patient data in 
a CSV or tab-delimited file for import, generation 
of the SF-36 scores and reports, and export of the 
calculated scores in a CSV or tab-delimited file 
for integration into SDTM/ADAM datasets.  
Missing data handling offered 
by SF-36 software will be 
used.  “Maximum Data 
Recovery” will be selected for 
Missing Score Estimator in the 
software.   
SF-36 change 
from baseline 
for domain 
and 
component 
Calculated as:  observed SF-36 score – baseline 
SF-36 score 
Missing if baseline or 
observed value is missing 


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Variable
Derivation/Comment
Imputation Approach if with 
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The SF-36 acute version will be used, 
which has a 1 week recall period.  
Responder Definitions were determined in 
the user’s manual (Maruish 2011).
scores
SF-36 
Domain score 
Responder 
Definition
Domain score increase (change from baseline) 
(1) Physical functioning >4.3;
(2) Role-physical > 4.0;
(3) Role-emotional >4.6;
(4) bodily pain >5.5;
(5) vitality >6.7;
(6) social functioning >6.2;
(7) mental health >6.7; and
(8) general health >7.0
Missing if baseline or 
observed value is missing
SF-36 PCS 
Responder 
Definition
PCS component score increase (change from 
baseline) >3.8
Missing if baseline or 
observed value is missing
SF-36 MCS 
Responder 
Definition
MCS component score increase (change from 
baseline) >4.6
Missing if baseline or 
observed value is missing
PatGA
The Patient’s Global Assessment of 
Psoriasis (PatGA) is a patient-reported, 
single-item scale on which patients are 
asked to rank, by selecting a number on a 
0-5 NRS, the severity of their psoriasis 
“today” from 0 (clear), no psoriasis, to 
5 (severe).
PatGA (0)
A PatGA assessed as 0
Missing if PatGA is missing
PatGA (0,1) 
and PatGA 
≥2 
improvement 
from baseline
A PatGA assessed as either 0 or 1, and the 
reduction (change from baseline) ≥2
Missing if baseline or 
observed value is missing
EQ-5D-
5L + Bolt 
On
The European Quality of Life–5 
Dimensions–5 Level (EQ-5D-5L) + Bolt 
On is a standardized measure of health 
status used to provide a simple, generic 
measure of health for clinical and 
economic appraisal.  The EQ-5D-5L 
consists of 2 components:  a descriptive 
system of the respondent’s health and a 
rating of his/her current health state using 
a 0- to 100-mm VAS.  
EQ-5D-5L + 
Bolt On Item 
Scores
Seven health profile dimensions, each dimension 
has 5 levels: 
1 = no problems
2 = slight problems
3 = moderate problems
4 = severe problems
5 = extreme problems  
It should be noted that the numerals 1-5 have no 
arithmetic properties and should not be used as a 
primary score.
Each dimension is a single 
item, missing if missing.  
Note: score of 9 is missing


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The descriptive system comprises the 
following 5 dimensions:  
Item 1:  mobility 
Item 2:  self-care 
Item 3:  usual activities 
Item 4:  pain/discomfort 
Item 5:  anxiety/depression 
The Bolt On is an addition to the EQ-5D-
5L that consists of 2 dimensions specific to 
psoriatic disease:  
Item 6:  skin irritation  
Item 7:  self-confidence   
The dimensions of Bolt On supplement the 
existing 5 dimensions of the EQ-5D in an 
attempt to better address specific burdens 
associated with psoriatic disease. 
The respondent is asked to indicate his/her 
health state by ticking (or placing a cross) 
in the box associated with the most 
appropriate statement in each of the 5 
dimensions.   
EQ-5D-5L 
UK 
population-
based index 
score  
Uses the concatenation of the value of each 
EQ-5D-5L dimension score in the order:  item 1; 
item 2; item 3; item 4; item 5.   
Derive EQ-5D-5L UK population-based index 
score according to the link by using the UK 
algorithm to produce a patient-level index score 
between -0.59 and 1.0 (continuous variable): 
https://euroqol.org/eq-5d-instruments/eq-5d-5l-
about/valuation-standard-value-sets/crosswalk-
index-value-calculator/ 
If any of the items is missing 
or coded as 9, the index score 
is missing.   
EQ-5D-PSO 
index score 
The value sets and psychometric properties of the 
EQ-5D + psoriasis Bolt On has been proposed 
and validated based on the UK population 
(Swinburn et al. 2013).  The psychometric 
analysis indicated the extra dimensions, skin 
irritation and self-confidence, successfully 
captured additional information for psoriasis 
patients. 
If any of the items is missing 
or coded as 9, the index score 
is missing. 
EQ-5D VAS 
Range from 0 = “worst imaginable health state” 
to 100 = “best imaginable health state” 
Note:  higher value indicates better health state. 
Single item, missing if 
missing 
Change from 
baseline of 
EQ-5D VAS 
or index 
scores 
Change from baseline = Observed score – 
Baseline score 
Missing if baseline or 
observed value is missing 
TSQM  
The Treatment Satisfaction Questionnaire 
for Medication (TSQM) is a self-
administered 9-item measure to evaluate 
patient treatment satisfaction with 
medication in 3 domains: 
Effectiveness 
Item 1:  prevention or treatment of 
TSQM 
Global 
Satisfaction 
Let “S” be the sum of all nonmissing items 7-9.  
TSQM Global Satisfaction is calculated as:  
100 ∗ሺܵെ3ሻ14
⁄
 
If either Item 7 or 8 is missing: 
100 ∗ሺܵെ2ሻ10
⁄
 
If Item 9 is missing: 
100 ∗ሺܵെ2ሻ8
⁄  
If more than 1 of the 3 items 
are missing, then missing 


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Measure 
Description 
Variable 
Derivation/Comment 
Imputation Approach if with 
Missing Components 
condition 
Item 2:  symptom relief 
Item 3:  time to start working 
Convenience 
Item 4:  difficulty of use 
Item 5:  difficulty in planning 
Item 6:  convenience 
Global Satisfaction 
Item 7:  confidence that medication is 
good 
Item 8:  certain that good outweighs 
bad 
Item 9:  overall satisfaction 
The recall period is the last 2-3 weeks or 
since the medication was last taken.  Item 
formats include both a 1- to 7-point and a 
1- to 5-point Likert scale.  Higher scores 
indicate greater satisfaction (Bharmal et al. 
2009).  
TSQM 
Effectiveness 
Let “S” be the sum of all nonmissing items 1-3.  
TSQM Effectiveness is calculated as:  
100 ∗ሺܵെ3ሻ18
⁄
 
If one item is missing: 
100 ∗ሺܵെ2ሻ12
⁄
If more than 1 of the 3 items 
are missing, then missing 
TSQM 
Convenience 
Let “S” be the sum of all nonmissing items 4-5.  
TSQM Effectiveness is calculated as:  
100 ∗ሺܵെ3ሻ18
⁄
 
If one item is missing: 
100 ∗ሺܵെ2ሻ12
⁄
 
If more than 1 of the 3 items 
are missing, then missing. 
QIDS-
SR16 
 
QIDS-SR16 is a self-administered, 16-item 
instrument intended to assess the existence 
and severity of symptoms of depression.  
A patient is asked to consider each item as 
it relates to the way they have felt over the 
last week.  There is a 4-point scale for each 
item ranging from 0 (best) to 3 (worst).   
The domains assessed by the instrument 
include:   
(1) sleep disturbance (initial, middle, and 
late insomnia or hypersomnia);  
(2) sad mood;  
QIDS-SR16 
Total Score 
The QIDS-SR16 total score is the sum of the 
domain scores below.  The total score has a range 
of 0-27.   
The total score will be missing 
if any domain score is 
missing. 
Sleep 
disturbance 
(initial, 
middle, and 
late insomnia 
or 
hypersomnia) 
The highest score recorded for the 4 sleep items:  
#1 (falling asleep), #2 (sleep during the night), #3 
(waking up too early) and #4 (sleeping too much) 
Domain is missing if all items 
are missing. 
Sad mood 
Item #5 (feeling sad) 
 
Domain is missing if the item 
is missing. 


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Measure
Description
Variable
Derivation/Comment
Imputation Approach if with 
Missing Components
(3) decrease/increase in appetite/weight; 
(4) concentration;
(5) self-criticism;
(6) suicidal ideation;
(7) interest;
(8) energy/fatigue;
(9) psychomotor agitation/retardation.  
Decrease /
increase in 
appetite /
weight
The highest score recorded for the 
appetite/weight items:  #6 (decreased appetite), 
#7 (increased appetite), #8 (decreased weight 
within the last two weeks), and #9 (increased 
weight within the last two weeks)
Domain is missing if all items 
are missing or not applicable.
Concentration
Item #10 (concentration / decision making)
Domain is missing if the item 
is missing.
Self-criticism
Item #11 (view of myself)
Domain is missing if the item 
is missing.
Suicidal 
ideation
Item #12 (thoughts of death or suicide)
Domain is missing if the item 
is missing.
Interest
Item #13 (general interest)
Domain is missing if the item 
is missing.
Energy /
fatigue
Item #14 (energy level)
Domain is missing if the item 
is missing.
Psychomotor 
agitation /
retardation
The highest score recorded for the two 
psychomotor items:  #15 (feeling slowed down) 
and #16 (feeling restless)
Domain is missing if all items 
are missing.
QIDS-SR16 
Response  
≥50% improvement in the QIDS-SR16 total score 
from baseline
If total score is missing for 
baseline or visit, then missing
QIDS-SR16 
Remission
QIDS-SR16 Total Score of 0-5
If total score is missing, then 
missing
Facial 
Psoriasis
Physician-assessed presence or absence of 
facial psoriasis.
Facial 
Psoriasis
Response is either Yes or No.
Missing if question is missing
Abbreviations:  ADaM = analysis data model; CSV = comma separated values; eCOA = electronic clinical outcomes assessment; EQ-5D = EuroQol 5 
Dimensions; EQ-5D-PSO = EuroQol 5 Dimensions – Psoriasis; MCS = Mental Component Score; NRS = Numeric Rating Scale; PCS = Physical Component
Score; Q = question; QIDS-SR16 = 16-item Quick Inventory of Depressive Symptomatology; QoL = quality of life; SDTM = study data tabulation model; 
SF-36 = Short Form 36-item Health Survey; sPGA = Static Physician Global Assessment; VAS = visual analog scale.


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Table AMAJ.6.6.
Description of Efficacy/Health Outcomes Analyses
Measure
Variable
Analysis Method
(Section 6.1.2)
Population
(Section 6.1.1)
Time Point and Period
PASI
PASI 90
(Primary and Sensitivity)
CMH analysis with NRI
ITT;
Induction PPS
Week 16 and all scheduled visits in 
Induction Period
ITT;
Induction and Maintenance PPS
Week 52 and all scheduled visits in 
Induction and Maintenance Periods
Logistic regression 
analysis with NRI
ITT
Week 16 and all scheduled visits in 
Induction Period
Tipping point analysis
ITT
Week 16
Categorical MMRM
ITT
Week 16 and all scheduled visits in 
Induction Period
PASI 75, 
PASI 100
CMH analysis with NRI
ITT
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
Time to first achieving PASI 100, 
PASI 90, or PASI 75 (i.e., 
3 different analyses)
KM analysis (censoring 
described in Table 
AMAJ.6.5)
ITT
All scheduled visits in Induction
Period
Maintenance of PASI 90 response
from Week 16 to Week 52
CMH analysis with NRI
ITT - Patients who are PASI 90 
Responders at Week 16
Week 52 and all scheduled visits in 
Maintenance Period
Maintenance of PASI 90 response 
from Week 24 to Week 52
CMH analysis with NRI
ITT - Patients who are PASI 90 
Responders at Week 24
Week 52 and all scheduled visits in 
Maintenance Period
Maintenance of PASI 100 response 
from Week 16 to Week 52
CMH analysis with NRI
ITT - Patients who are PASI 100 
Responders at Week 16
Week 52 and all scheduled visits in 
Maintenance Period
Maintenance of PASI 100 response 
from Week 24 to Week 52
CMH analysis with NRI
ITT - Patients who are PASI 100 
Responders at Week 24
Week 52 and all scheduled visits in 
Maintenance Period
Stability of PASI 90 up to Week 
52 from Week 16
CMH analysis with NRI
ITT
All scheduled visits in Maintenance 
Period
ITT - Patients who are PASI 90 
Responders at Week 16
All scheduled visits in Maintenance
Period
Stability of PASI 100 up to Week 
52 from Week 16
CMH analysis with NRI
ITT
All scheduled visits in Maintenance 
Period
ITT - Patients who are PASI 100 
Responders at Week 16
All scheduled visits in Maintenance
Period


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Description of Efficacy/Health Outcomes Analyses
Measure
Variable
Analysis Method
(Section 6.1.2)
Population
(Section 6.1.1)
Time Point and Period
PASI
Cumulative time with PASI 90 
response from Week 16 to Week 
52:
AUCs of PASI 90 response over 
time; 
Percentages of scheduled visits 
with PASI 90 response;
Percentages of weeks with PASI 
90 response
ANCOVA with factors:  
treatment, PASI baseline 
value, biologic therapy, 
body weight and 
geographic region
ITT - Patients who are PASI 90 
Responders at Week 16
All scheduled visits in Maintenance 
Period
Cumulative time with PASI 90 
response from Week 0 to Week 52:
AUCs of PASI 90 response over 
time; 
Percentages of scheduled visits 
with PASI 90 response;
Percentages of weeks with PASI 
90 response
ANCOVA with factors:  
treatment, PASI baseline 
value, biologic therapy, 
body weight and 
geographic region
ITT
All scheduled visits in Induction and 
Maintenance Periods
PASI ≤5;
PASI ≤3;
PASI ≤2;
PASI ≤1
CMH analysis with NRI
ITT
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
PASI change from baseline
MMRM; 
ANCOVA with mBOCF
ITT
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
Percentage improvement from 
baseline
MMRM; 
ANCOVA with mBOCF
ITT
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
sPGA
sPGA (0,1)
(Primary and Sensitivity)
CMH analysis with NRI
ITT;
Induction PPS
Week 16 and all scheduled visits in 
Induction Period
ITT;
Induction and Maintenance PPS
Week 52 and all scheduled visits in 
Induction and Maintenance Periods
Logistic regression 
analysis with NRI
ITT
Week 16 and all scheduled visits in 
Induction Period
Categorical MMRM
ITT
Week 16 and all scheduled visits in 
Induction Period


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Description of Efficacy/Health Outcomes Analyses
Measure
Variable
Analysis Method
(Section 6.1.2)
Population
(Section 6.1.1)
Time Point and Period
sPGA
Tipping point analysis
ITT
Week 16
sPGA (0)
CMH analysis with NRI
ITT
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
Time to first achieving sPGA (0,1)
or sPGA (0) (i.e., 2 different 
analyses)
KM product limit curve 
(censoring described in 
Table AMAJ.6.5)
ITT
All scheduled visits in Induction Period
BSA
Proportion of patients with ≤1% of 
BSA with psoriasis involvement
CMH analysis with NRI
ITT
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
BSA change from baseline
MMRM; 
ANCOVA with mBOCF
ITT
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
PSS
PSS Symptoms Score of 0;
PSS Signs Score of 0
CMH analysis with NRI
ITT - Patients with Baseline PSS 
Symptoms Score ≥1 and PSS 
Signs Score ≥1, respectively
All scheduled weeks in Induction Period;
All scheduled weeks/visits in Induction 
and Maintenance Periods
Change from baseline for PSS
Symptoms Score, Signs Score, and
Item Scores
MMRM; 
ANCOVA with mBOCF
ITT 
All scheduled weeks in Induction Period;
All scheduled weeks/visits in Induction 
and Maintenance Periods
PSSI
PSSI change from baseline
MMRM; 
ANCOVA with mBOCF
ITT - Patients with Scalp 
Involvement at Baseline
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
PSSI score = 0 
CMH analysis with NRI
ITT - Patients with Scalp 
Involvement at Baseline
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
PPASI
PPASI change from baseline 
MMRM; 
ANCOVA with mBOCF
ITT - Patients with Palmoplanter 
Involvement at Baseline
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
PPASI 50;
PPASI 75;
PPASI 100;
CMH analysis with NRI
ITT - Patients with Palmoplanter 
Involvement at Baseline
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
NAPSI
NAPSI change from baseline
MMRM; 
ANCOVA with mBOCF
ITT - Patients with Nail 
Psoriasis Involvement at 
Baseline
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods


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Description of Efficacy/Health Outcomes Analyses
Measure
Variable
Analysis Method
(Section 6.1.2)
Population
(Section 6.1.1)
Time Point and Period
NAPSI
NAPSI score = 0
CMH analysis with NRI
ITT - Patients with Nail 
Psoriasis Involvement at 
Baseline
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
DLQI
DLQI (0,1) and ≥5-point reduction 
from baseline
CMH analysis with NRI
ITT - Patients with Baseline 
DLQI ≥5 
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
DLQI (0,1)
CMH analysis with NRI
ITT - Patients with Baseline 
DLQI >1
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
DLQI total score ≥5-point 
reduction from baseline
CMH analysis with NRI
ITT - Patients with Baseline 
DLQI ≥5
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
DLQI total score and domain 
scores change from baseline
MMRM; 
ANCOVA with mBOCF
ITT 
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
SF-36
SF-36 change from baseline for
PCS and MCS Component Scores
and Domain Scores
ANCOVA with mBOCF
ITT 
Last visit in Induction Period
MMRM;
ANCOVA with mBOCF
ITT
All scheduled visits in Induction and 
Maintenance Periods
SF-36 PCS Responder Definition; 
SF-36 MCS Responder Definition; 
SF-36 Domain score Responder 
Definition;
CMH analysis with NRI
ITT
Last visit in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
PatGA
PatGA(0)
CMH analysis with NRI
ITT - Patients with Baseline 
PatGA >0
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
PatGA (0,1) and ≥2-point
improvement from baseline
CMH analysis with NRI
ITT - Patients with Baseline 
PatGA ≥2
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
WPAI-PSO
Change from baseline in WPAI-
PSO Scores (Absenteeism,
Presenteeism, Work Productivity,
Activity Impairment)
ANCOVA with mBOCF
ITT - Patients with Baseline 
Employment Status of Yes
Last visit in Induction Period
MMRM;
ANCOVA with mBOCF
ITT - Patients with Baseline 
Employment Status of Yes
All scheduled visits in Induction and 
Maintenance Periods


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Description of Efficacy/Health Outcomes Analyses
Measure
Variable
Analysis Method
(Section 6.1.2)
Population
(Section 6.1.1)
Time Point and Period
TSQM
Mean Effectiveness, Convenience, 
and Global Satisfaction
ANCOVA with mBOCF
ITT
Last visit in Induction Period
MMRM;
ANCOVA with mBOCF
ITT
All scheduled visits in Induction and 
Maintenance Periods
EQ-5D-5L + 
Bolt On
Change from baseline of EQ-5D
VAS and Index scores
MMRM; 
ANCOVA with mBOCF
ITT
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
EQ-5D Dimension Scores with no 
problems
CMH analysis with NRI
ITT
All scheduled visits in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
QIDS-SR16
QIDS-SR16 Response;
QIDS-SR16 Remission
CMH analysis with NRI
ITT - Patients with Baseline 
Value ≥11
Last visit in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
Facial 
Psoriasis
Facial Psoriasis
Summary statistics;
Shift table
ITT
Last visit in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
Absence of Facial Psoriasis
CMH analysis with NRI
ITT - Patients with Baseline 
Facial Psoriasis
Last visit in Induction Period;
All scheduled visits in Induction and 
Maintenance Periods
Abbreviations:  AUC = area under the curve; ANCOVA = analysis of covariance; BSA = body surface area; CMH = Cochran-Mantel-Haenszel; DLQI = Global 
Assessment Dermatology Life Quality Index; E5-5D = EuroQoL 5 Dimensions; EQ-5D-5L = EuroQoL–5 Dimensions–5 Level; ITT = intent-to-treat; KM = 
Kaplan-Meier; mBOCF = modified baseline observation carried forward; MCS = Mental Component Score; MMRM = mixed model repeating measures; 
NAPSI = Nail Psoriasis Severity Index; NRI = nonresponder imputation; PASI = Psoriasis Area and Severity Index; PASI 75/90/100 = 75%/90%/100% 
improvement in PASI from baseline; PatGA = Patients Global Assessment of Psoriasis; PCS = Physical Component Score; PPASI = Palmoplantar Psoriasis 
Severity Index; PPS = per protocol set; PSS = Psoriasis Symptoms Scale; PSSI = Psoriasis Scalp Severity Index; QIDS-SR16 = a self-administered, 16-item
instrument to assess symptoms of depression; SF-36 = a 36-item, patient-completed measure designed to assess health; sPGA = Static Physician Global 
Assessment; TSQM = Treatment Satisfaction Questionnaire for Medication; WPAI-PSO = Work Productivity and Activity Impairment - Psoriasis.


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6.11.1. Primary Outcome and Methodology
Primary outcome PASI 90 and sPGA (0,1) and their analysis are described in Table AMAJ.6.5
and Table AMAJ.6.6.
6.11.2. Major Secondary Efficacy Analyses 
Major secondary outcomes and their analyses are described in Table AMAJ.6.5 and Table 
AMAJ.6.6.
6.11.3. Other Secondary Efficacy Analyses
Other secondary outcomes and their analyses are described in Table AMAJ.6.5 and Table 
AMAJ.6.6.
6.11.4. Sensitivity Analyses 
Sensitivity analyses for both primary and secondary endpoints are described in Table AMAJ.6.5
and Table AMAJ.6.6.
6.12. Health Outcomes/Quality-of-Life Analyses 
Analyses of PSS, Global Assessment Dermatology Life Quality Index (DLQI), Patients Global 
Assessment of Psoriasis (PatGA), Work Productivity and Activity Impairment-Psoriasis (WPAI-
PSO), TSQM, EQ-5D-5L + Bolt on, QIDS-SR16 and SF-36 health outcomesare described in 
Table AMAJ.6.5 and Table AMAJ.6.6.
6.13. Bioanalytical and Pharmacokinetic/Pharmacodynamic Methods 
Details of PK/pharmacodynamic (PD) analyses can be found in a separate PK/PD analysis plan.
6.14. Safety Analyses
The planned analyses of safety data will be performed with an intent to maintain consistency 
with compound level standard safety analyses.  These standards are based on internal standards 
which were informed by Clinical Data Interchange Standards Consortium (CDISC) standards, 
regulatory guidance (for example, FDA Clinical Review Template), and cross-industry 
standardization efforts (for example, Pharmaceutical Users Software Exchange [PhUSE] white 
papers from the Standard Analyses and Code Sharing Working Group provided in the PhUSE 
Computational Science Deliverables Catalog [WWW]).
In general, safety evaluations will be based upon the following safety analysis populations with 
their associated study periods:

Induction Safety Population

All Active Treatment Safety Population
These analysis populations are fully defined in Table AMAJ.6.1, while Table AMAJ.6.2
describes the treatment groups, associated study periods and the comparisons for each analysis 
population. 


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Unless otherwise noted, Fisher’s exact test will primarily be used to compare percentages, and 
odds ratios will be provided.  Odds ratios will be created with mirikizumab treatment as the 
numerator, and placebo or secukinumab as the denominator.  
Treatment differences in mean change for continuous measurements will be assessed using an 
ANCOVA model containing terms for treatment and the continuous covariate of baseline 
measurement.  Type 3 sums of squares will be used.  The significance of within-treatment group 
changes from baseline will be evaluated by testing whether the treatment group LS mean 
changes from baseline are different from zero using a t-statistic.  
Not all displays described in this section will necessarily be included in the CSRs.  Any display 
described and not provided in the CSR would be available upon request.  Not all displays will 
necessarily be created as a “static” display.  Some may be incorporated into interactive display 
tools instead of or in addition to a static display.  Any display created interactively will be 
included in the CSR if deemed relevant to the discussion.  
6.14.1. Extent of Exposure
Duration of exposure to study treatment will be summarized by treatment group for each of the 
2 safety analysis populations (that is, Induction Safety and All Active Treatment Safety).  For the 
treatment period of interest associated with each safety analysis population, exposure will be 
calculated as the time period length in years (see Section 6.1.1.1) with start and end dates 
described in Table AMAJ.6.3. The following periods will be used for calculations:

For the Induction Safety Population, the Induction Period Interval will be used.

For the All Active Treatment Safety Population, 1) for patients randomized to 
mirikizumab and secukinumab, the Induction and Maintenance Period Interval will be 
used; 2) for patients randomized to placebo and entering the Maintenance Period, the 
Maintenance Period Interval will be used.
Total patient-years (PY) of exposure will be reported for both safety analysis populations by 
treatment group (see Table AMAJ.6.2).  Descriptive statistics will be provided for patient-weeks 
of exposure and the frequency of patients falling into different exposure ranges will be 
summarized:  

>0, ≥4 weeks, ≥8 weeks, ≥12 weeks, ≥16 weeks, ≥ 24 weeks, ≥32 weeks, ≥40 weeks, 
≥48 weeks

>0 to <4 weeks, ≥4 weeks to <8 weeks, ≥8 weeks to <12 weeks, ≥12 weeks to 
<16 weeks, …, ≥48 weeks
Additional exposure ranges may be considered if necessary.  No p-values will be reported in 
these tables as they are intended to describe the study populations, rather than test hypotheses 
about them.


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6.14.2. Adverse Events
A treatment-emergent adverse event (TEAE) is defined as an event that first occurred or 
worsened in severity after baseline.  The MedDRA Lowest Level Term (LLT) will be used in the 
treatment-emergent computation.  The maximum severity for each LLT during the baseline 
period will be used as baseline.  The treatment period will be included as postbaseline for the 
analysis.  For events with a missing severity during the baseline period, it will be treated as 
‘mild’ in severity for determining treatment-emergence.  Events with a missing severity during 
the postbaseline period will be treated as ‘severe’ and treatment-emergence will be determined 
by comparing to baseline severity.  For events occurring on the day of first taking study 
medication, the start times of the study treatment and AE will be used to determine whether the 
event was pre- versus posttreatment.  If start time for the AE is missing, it will be assumed to 
have started in the later period.
Summary tables as described in Table AMAJ.6.7 will be presented for the 2 safety 
populations/periods as indicated.  Summary tables will include the number and percentage of 
patients reporting an event.  For events that are gender-specific (as defined by MedDRA), the 
number of participants at risk will include only patients from the given gender.  Comparisons 
will be performed using Fisher’s exact test.  For document writing purposes, tests with 2-sided p-
values less than 0.05 will be referred to as “having strong evidence for a treatment difference”, 
unless otherwise noted.  However, p-values should not be over interpreted for these safety 
analyses.  Except for prespecified hypotheses, they correspond to data-driven hypotheses and 
hence are only useful as a flagging mechanism.
For the 2 safety populations, the baseline period and postbaseline will be defined as follows:

Induction Safety Population:  The baseline period is the Screening Period.  The 
postbaseline period will be the Induction Period.

All Active Treatment Safety Population:  The baseline period for patients randomized 
to mirikizumab and secukinumab during induction is the Screening Period.  For
patients randomized to placebo, the baseline events are those events which are 
ongoing at the time of the first injection with mirikizumab (that is, the baseline period 
is a moment in time).  Two different postbaseline periods will be used:
o
For “all miri” and “all secu”, the All Active Treatment Periods will be used.
o
For “all miri + follow-up” and “all secu + follow-up”, the All Active Treatment 
and Follow-Up Periods will be used.


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Table AMAJ.6.7.
Summary Tables Related to Adverse Events
Analysis
Population
Overview of AEs
I, A
Summary of TEAE PTs by decreasing frequency
I, A
Summary of TEAE PTs occurring in ≥1% of patients by decreasing frequency
I, A
Summary of TEAE PTs by decreasing frequency within SOC
I, A
Summary of TEAE PTs by maximum severity by decreasing frequency
I, A
Summary of SAE PTs by decreasing frequency
I, A
Summary of AEs leading to treatment discontinuation
I, A
Listing of SAEs 
ITT
Listing of Deaths
All Entered 
Patients
Abbreviations:  A = All Active Treatment Safety; AE = adverse event; I = Induction Safety; ITT = Intent-to-Treat; 
PT = preferred term; SAE = serious adverse event; SOC = System Organ Class; TEAE = treatment-emergent 
adverse event.
6.14.2.1. Common Adverse Events
The percentages of patients with TEAEs will be summarized by treatment using MedDRA PT 
for the common TEAEs (reported in ≥1% before rounding of treated patients).  Events will be 
ordered by decreasing frequency in the all treatment group.  See Table AMAJ.6.7.
6.14.2.2. Deaths, Other Serious Adverse Events, and Other Notable Adverse 
Events
The number and percentage of patients reported with an SAE during the treatment period will be 
summarized by treatment using MedDRA PT.  Events will be ordered by decreasing frequency 
in the all treatment group.  This analysis will be conducted for the 2 safety populations.  A listing 
of SAEs will be provided.
The number and percentage of patients who permanently discontinued from study treatment due 
to an AE (including AEs that led to death) during the treatment period will be summarized by 
treatment using MedDRA PT.  Events will be ordered by decreasing frequency in the all 
treatment groups.  This analysis will be conducted for the 2 safety populations.
6.14.3. Clinical Laboratory Evaluation
As described more fully in compound level safety standards and in the laboratory-related PhUSE 
white papers (PhUSE 2013; PhUSE 2015), the clinical laboratory evaluations will be 
summarized with the following displays described in Table AMAJ.6.8.


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Table AMAJ.6.8.
Summaries/Displays/Analysis for Clinical Laboratory Evaluations
Analysis
Population
Box plots of observed values (and change from baseline values) by visit. Change from 
baseline to last observation will be summarized within the box plot of changes (rightmost 
column), and descriptive summary statistics will be included in a table below the box plot 
along with a p-value using the ANCOVA model described in Section 6.14.
I, Aa
Treatment-emergent abnormal high lab values (i.e., patients shifting from a normal/low 
maximum baseline value to a high maximum postbaseline value) or low lab values (i.e.,
patients shifting from normal/high minimum baseline value to a low minimum 
postbaseline value)
I, A
Scatter plot of maximum (minimum) postbaseline value vs maximum (minimum) baseline 
value
I, A
Shift tables showing the number of patients who shift from each category of maximum 
(minimum) baseline observation to each category of maximum (minimum) postbaseline 
observation.  Here categories may be low, normal, or high with cut-offs defined in the 
compound level safety standards.
I, A
Abbreviations:  A = All Active Treatment Safety; ANCOVA = analysis of covariance; I = Induction Safety.
a
Excluding placebo/250 miri treatment group for all active treatment safety population.
For these displays, the postbaseline periods will be identical to those described in Section 6.14.2.  
Postbaseline measurement for continuous analysis (for example, boxplots) will include only
scheduled measurements, while postbaseline categorical analysis (for example, shifts) will 
include both scheduled and unscheduled measurements.
Measurements are defined to be in the baseline periods as follows:

Induction Safety Population:
o
For analyses of continuous measurements:  the last scheduled or 
unscheduled nonmissing measurement recorded during the Screening 
Period.
o
For analyses of categorical measurements:  all scheduled or unscheduled 
nonmissing measurements recorded during the Screening Period.

All Active Treatment Safety Population:
o
For analyses of continuous measurements:  (1) the last scheduled or 
unscheduled nonmissing measurement recorded during the Screening 
Period for the patients randomized to mirikizumab and secukinumab, (2) 
the last scheduled or unscheduled nonmissing measurement recorded 
before first miri treatment for patients randomized to placebo.  
o
For analyses of categorical measurements:  (1) all scheduled or 
unscheduled nonmissing measurements recorded during the Screening 
Period for the patients randomized to mirikizumab and secukinumab, (2) 
the last scheduled or unscheduled nonmissing measurement recorded 
before first miri treatment for patients randomized to placebo.
For any lab given on the day of first taking study medication at the start of the postbaseline 
period, the start time of the study treatment will be used to determine whether the lab was pre-


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versus postbaseline.  If time for the lab is missing, it will be assumed to be in the baseline period 
(that is, we assume the protocol defined order of procedures was followed).  Following the 
compound level safety standards, for some labs a safety concern may exist for only high (or only 
low) values.  For these labs, displays with only maximum (or minimum) values will be used and 
shift tables will be presented accordingly.
6.14.4. Vital Signs and Other Physical Findings
As described more fully in compound level safety standards and in the vital signs-related PhUSE 
white papers (PhUSE 2013; PhUSE 2015), vital signs will be summarized similarly to the 
clinical laboratory evaluation (see Section 6.14.4).  For vital signs, the low and high limits are 
based on a combination of a specified value and a change or percentage change as defined in the 
compound level safety standards.  In this case, the PhUSE white paper recommends providing 
scatter plots and shifts to low/high.  Boxplots will also be presented.  
6.14.5. Electrocardiograms
Complete electrocardiogram (ECG) data will not be part of the clinical database.  Any clinically 
significant findings from ECGs that result in a diagnosis and that occur after the patient receives 
the first dose of the investigational treatment will be reported as an AE via eCRF.  Aside from 
standard AE summary tables no additional analysis of ECG data will be performed.
6.14.6. Immunogenicity
An individual sample is potentially examined multiple times in a hierarchical procedure to 
produce a sample antidrug antibodies (ADA) assay result and potentially a sample neutralizing 
antidrug antibodies (NAb) assay result.  A patient has treatment-emergent antidrug antibodies 
(TE-ADA) when ADAs are induced or boosted by exposure to study drug; that is, when at least 
1 postbaseline ADA sample has a 4-fold increase in titer compared to baseline (if ADAs were 
present at baseline) or has a titer 2-fold greater than the minimum required dilution of 1:10 (if no 
ADAs were present at baseline).
Compound level safety standards will be followed in the analyses of immunogenicity.  Listings 
of immunogenicity assessments will be provided along with the summary of specified TEAEs by 
TE-ADA status.  The summary of TE-ADA and NAb status will be produced for the 2 safety 
populations, where the postbaseline period for reporting is the same as described for AEs in 
Section 6.14.2.  The subgroup analysis of efficacy by TE-ADA status (positive, negative) is 
described in the Section 6.15.  Additional assessments of the relationship between 
immunogenicity and efficacy will be performed as part of the integrated analysis including other 
Phase 3 mirikizumab psoriasis trials.
6.14.7. Special Safety Topics including Adverse Events of Special 
Interest 
This section includes areas of interest whether due to observed safety findings, potential findings 
based on drug class, or safety topics anticipated to be requested by a regulatory agency for any
reason.  In general, potential adverse events of special interest (AESI) relevant to these special 


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safety topics will be identified by one or more standardized MedDRA query(ies) (SMQs), by a 
Lilly defined MedDRA PT listing based upon the review of the most current version of 
MedDRA, or by treatment-emergent relevant laboratory changes, as described below.  
Additional special safety topics may be added as warranted.  
Unless otherwise specified, the AESIs will be summarized for the 2 safety populations during 
their associated study periods using the baseline and postbaseline definitions described in 
Sections 6.14.2 and 6.14.3.
Full details of the search terms and rules for deriving AESIs in each of the sections below are 
described in the compound level safety standards along with information about the types of 
summaries and listings to be provided.
6.14.7.1. Hepatic Safety
Hepatic labs include alanine aminotransferase (ALT) and aspartate transaminase (AST), total 
bilirubin (TBL) and serum alkaline phosphatase (ALP).  When criteria are met for hepatic 
evaluations, investigators will complete a follow-up Hepatic Safety eCRF.  
Analyses will include:

ALT and AST:  The percentages of patients with a measurement greater than or equal 
to 3 times (3X), 5 times (5X), and 10 times (10X) the Covance upper limit of normal 
(ULN) during the treatment period for all patients with a postbaseline value and for 
subsets based on various levels of baseline value.  

TBL and ALP:  The percentages of patients with a measurement greater than or equal 
to 2 times (2X) the Covance ULN during the treatment period will be summarized for 
all patients with a postbaseline value and for subsets based on various levels of 
baseline value.  

Plot of maximum postbaseline ALT versus maximum postbaseline TBL (Induction 
Safety Population for All Periods:  ever on miri and never on miri).

A listing of the information collected on the Hepatic-Safety eCRF.
6.14.7.2. Infections, including opportunistic infections and serious infections
Infections will be defined using the PTs from the MedDRA Infections and Infestations SOC.  
Treatment-emergent infections will be analyzed for:  all infections (by maximum severity), 
serious infections and opportunistic infections (OI).  The MedDRA terms used to identify 
infections considered to be OI in patients with immune mediated inflammatory conditions treated 
with immunomodulatory drugs are based on Winthrop et al. (2015) and are listed in the 
compound level safety standards.  The list contains narrow (more specific) and broad (less 
specific) PTs with respect to these prospectively defined OIs.  
Analyses will include:

treatment-emergent infections by PT

serious infections by PT

OI:  treatment-emergent OI by narrow terms and broad terms separately


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6.14.7.3. Hypersensitivity
Hypersensitivity reactions is used as an overarching term to describe events that are systemic or 
localized reactions that likely have an allergic/hypersensitivity etiology.  Patients will be 
evaluated by the investigator for signs and symptoms suggestive of hypersensitivity and 
investigators will complete a follow-up eCRF designed to record additional information.  
Potential hypersensitivity reactions will be determined using the following SMQs:  anaphylactic 
reaction, hypersensitivity, and angioedema.  Potential hypersensitivity will be categorized as 
immediate (that is, occurring within 24 hours) and non-immediate (that is, occurring after the day 
of study drug administration but prior to subsequent drug administration) based on the timing of 
the reaction.  
Analyses will include:

for immediate hypersensitivity: (1) combined narrow/algorithmic search (that is, any 
narrow term from any one of the SMQs, or anaphylaxis algorithm); (2) narrow search 
(that is, any narrow term) by SMQ; (3) broad search (that is, any narrow or broad 
term) by SMQ; and (4) TEAEs (occurring on the day of study drug administration) by 
PT not in any of the 3 SMQs

for nonimmediate hypersensitivity: (1) combined narrow search (that is, any narrow 
term from any one of the SMQs); (2) narrow search (that is, any narrow term) by 
SMQ; and (3) broad search (that is, any narrow or broad term) by SMQ
6.14.7.4. Injection Site Reactions (ISR)
Injection site reactions (ISRs) are AEs localized to the immediate site of the administration of a 
drug.  The evaluation of study drug related ISRs will be through the unsolicited reporting of ISR 
TEAEs and through the use of an Injection Site Reaction Follow-up Form completed by the 
investigator for each ISR reported. 
Injection site reactions will be defined using the MedDRA High Level Term (HLT) of Injection 
Site Reaction, excluding certain PTs (for example, those PTs related to injections into a joint).  
Analyses will include:

TE ISRs by PT.

The additional data collected on the ISR follow-up form will be summarized in 2
distinct ways:  at the patient level and at the event level.  A by-patient listing of these 
data will be provided.
6.14.7.5. Cerebro-Cardiovascular Events
The cerebro-cardiovascular events reported in the study will be adjudicated by an independent, 
external adjudication committee (AC).  All confirmed events after adjudication will be used for 
the analysis of cerebro-cardiovascular events.  Categories of events include:  Cardiovascular, 
Cerebrovascular and Peripheral Vascular Events.  As detailed in the compound level safety 
standards, the categories are further categorized into subcategories.


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Analyses will include:

TE cerebro cardiovascular confirmed events by category, subcategory, and PT.

By-patient listing for all patients having a TEAE of cerebro-cardiovascular 
(confirmed event, no event, or insufficient documentation for event determination) at 
any time.
6.14.7.6. Malignancies
Malignancies will be defined using PTs from the Malignant tumors SMQ.  Malignant tumor 
events will be summarized separately for the categories:  Non-Melanoma skin cancer (NMSC) 
and Malignancies excluding NMSC.
Analyses will include:

TE malignancy by category and PT.

By-patient listing for all patients having a TEAE of malignancy at any time.
6.14.7.7. Suicidal Ideation/Behavior and Depression 
During the study, suicidal ideation and behavior, and depression will be assessed prospectively 
by the investigator via signs and symptoms and through the use of the Columbia-Suicide 
Severity Rating Scale (C-SSRS) and the QIDS-SR16.  Analyses will include:

C-SSRS:  Only a listing of the C-SSRS will be provided.  Additional summaries may 
be provided if justified by the number of events (further described in the compound 
level safety standards). 

QIDS-SR16:  Shift tables will be provided showing the number and percentage of 
patients within each baseline category (maximum value) versus each postbaseline 
category (maximum value) by treatment.  Additionally, outcomes such as any 
increase in depression will be compared between treatments (further described in the 
compound level safety standards).
6.15. Subgroup Analyses
6.15.1. Efficacy Subgroup Analyses
Subgroup analyses will be conducted for the primary endpoints of Week 16 PASI 90 and 
sPGA (0,1) proportion in the ITT Population.  Also, subgroup analysis for the Week 52 PASI 90 
and sPGA (0,1) proportion in the ITT population will be performed.  The subgroups to be 
analyzed are listed in Table AMAJ.6.4 along with the demographic characteristics.  Some 
additional subgroup analyses may be performed to meet regulatory requirements in specific 
countries.  Additional subgroup analyses, which are not based on baseline/demographic 
characteristics in Table AMAJ.6.4 are:  

concomitant topical steroid product use:  yes, no.  

concomitant systemic corticosteroid use:  yes, no

treatment-emergent antimirikizumab antibody status: positive, negative


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The analysis of additional subgroups will not require an amendment to the SAP.  Missing 
outcome data will be imputed using NRI.  Within each subgroup category the proportion of 
responders by treatment, treatment differences and 95% CIs will be displayed.  Also, p-values 
using Fisher’s exact test for treatment comparison will be provided.  If the number of patients in 
any subgroup category is <10% of the total population, only summaries of the efficacy data will 
be provided (that is, no inferential testing).  Forest plots will be generated to display the odds 
ratios and 95% CIs for the efficacy subgroup analyses.
A logistic regression model with treatment, subgroup, and the interaction of subgroup by
treatment will be used.  The subgroup-by-treatment interaction will be tested using the Firth 
correction (Firth 1993) at the significance level of 0.10.  
6.15.2. Safety Subgroup Analyses
Subgroup analysis for safety related endpoints will be performed within the context of the 
integrated safety analysis.  No safety subgroup analysis will be performed specifically for this 
study unless there is a potentially relevant finding during the periodic study safety reviews.
6.16. Analysis for Japan Submission
A subset of the planned efficacy, health outcomes and safety analyses will be reproduced based 
on patients from Japan sites, in support of the regulatory submission in Japan. The list of tables, 
listings, and figures for the patients from Japan sites (Japanese population) will be in a separate 
document. 
Protocol Addendum I6T-MC-AMAJ (1.1) is performed in Japan to enable the inclusion of 
patients with generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) to fufill the 
needs for Japan submission.  Appendix 2 provides the details of the Analysis Plan for the Japan 
Addendum. 
6.17. Analysis for Australian Submission
In addition to the analysis already specified, a subset of planned efficacy analyses will be 
conducted to meet the Pharmaceutical Benefits Advisory Commission (PBAC) criteria.  The 
PBAC population is a subset of the patients with a PASI score >15 at baseline in the ITT 
Population. The sPGA (0,1), sPGA (0), PASI 75, PASI 90 and PASI 100 using the PBAC 
population will be analyzed for Induction Period, and combined Induction and Maintenance 
Periods.  
6.18. Protocol Deviations
Protocol deviations will be identified throughout the study.  Important protocol deviations are 
defined as those deviations from the protocol likely to have a significant impact on the 
completeness, accuracy, and/or reliability of the study data or that may significantly affect a 
patient’s rights, safety, or well-being.  
The major protocol deviations, which are the subset of the important protocol deviations, are the 
protocol deviations that might have impact on the efficacy and/or safety results.  The impact of 


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major protocol deviations on the efficacy results will be investigated by assessing the robustness
of the study results and conclusions to the choice of analysis population, both by including and 
excluding the data potentially affected by major protocol deviations.  
A separate document known as the “The AMAJ Trial Issues Management Plan” describes the
categories and subcategories of important protocol deviations, whether or not these deviations 
are major protocol violations, the action to be taken regarding the exclusion of patients from PPS 
and the source of the deviation identified.  
The number and percentage of patients having important protocol deviation(s) will be 
summarized within category and subcategory of deviations by treatment for the ITT population 
in the Induction Period and the combined Induction and Maintenance Periods.
A by-patient listing of important protocol deviations will be provided.
6.19. Interim Analyses and Data Monitoring 
Data Monitoring Committee:  One DMC consisting of members external to Lilly will be 
established for interim safety monitoring across Studies I6T-MC-AMAK, AMAJ, and AMAH in 
patients with psoriasis.  This committee will consist of a minimum of 3 members, including a 
physician with expertise in dermatology and a statistician.  No member of the DMC may have 
contact with study sites.  A Statistical Analysis Center (SAC) will prepare and provide unblinded 
safety data to the DMC.  The SAC members may be Lilly employees or from third-party 
organizations designated by Lilly.  However, they will be external to the study team and will 
have no contact with sites and no privileges to influence change in the ongoing study.  Access to 
the unblinded safety data will be limited to the DMC and the SAC or their designees.  The study 
team will not have access to the unblinded data.  Only the DMC is authorized to evaluate 
unblinded data.  The purpose of the DMC is to advise Lilly regarding continuing patient safety; 
however, the DMC may request key efficacy data to put safety observations into context and to 
confirm a reasonable benefit/risk profile for ongoing patients in the study.  Hence, there will be 
no alpha adjustment for these interim assessments.  Study sites will receive information about 
interim assessments ONLY if they need to know for the safety of their patients.  This committee 
will make recommendations as to whether it is scientifically and ethically appropriate to continue 
enrollment, discontinue a treatment group, or discontinue the study.  Details outlining the roles 
and responsibilities of the DMC will be finalized in the DMC charter and an associated DMC 
analysis plan prior to the first unblinded assessment.  
Week 52 Database lock (DBL): An unblinded analysis will be performed after all patients have 
completed the Week 52 Visit or discontinued study treatment.  This DBL will include all data 
collected by the cut-off date including follow-up data from patients that have begun the 
Posttreatment Follow-Up Period.  This is the final analysis for the efficacy endpoints up to 
Week 52.  However, the study may be ongoing for the Posttreatment Follow-Up Period at the 
time of this DBL.
Final DBL: A final DBL will occur after the Posttreatment Follow-Up Period is completed.  


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Pharmacokinetics Analysis: In addition, a limited number of preidentified internal Lilly 
personnel that are not in contact with clinical sites may gain access to unblinded data including 
PK, as specified in the unblinding plan, after all patients have completed Week 40 visit or 
discontinued study treatment, in order to initiate the population PK model development 
processes.  The unblinded data will be restricted and will NOT be shared with anyone outside 
this preidentified group until after the Week 52 DBL. Unblinding details will be provided in the 
unblinding plan.
6.20. Annual Report Analyses
Based on regulatory requirements for the Development Safety Update Report (DSUR), reports 
will be produced (if not already available from the study CSR) for the reporting period covered 
by the DSUR.
6.21. Clinical Trial Registry Analyses
Additional analyses will be performed for the purpose of fulfilling the Clinical Trial Registry 
(CTR) requirements.  
Analyses provided for the CTR requirements include the following:
Summary of AEs, provided as a dataset which will be converted to an XML file.  Both Serious 
Adverse Events (SAEs) and ‘Other’ AEs are summarized:  by treatment group, by MedDRA PT.

An AE is considered ‘Serious’ whether or not it is a TEAE.

An AE is considered in the ‘Other’ category if it is both a TEAE and is not serious.  
For each SAE and ‘Other’ AE, for each term and treatment group, the following are 
provided:
o
the number of participants at risk of an event
o
the number of participants who experienced each event term
o
the number of events experienced.

Consistent with www.ClinicalTrials.gov requirements, ‘Other’ AEs that occur in 
fewer than 5% of patients/subjects in every treatment group may not be included if a 
5% threshold is chosen (5% is the minimum threshold).

AE reporting is consistent with other document disclosures for example, the CSR, 
manuscripts, and so forth.  


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7.
Unblinding Plan
Unblinding details are specified in a separated unblinding plan.  


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8.
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Alosh, M., Bretz, F. and Huque, M. Advanced multiplicity adjustment methods in clinical trials. 
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and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with 
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safety of mirikizumab (LY3074828) in the treatment of moderate-to-severe plaque psoriasis: 
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9.
Appendices


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Appendix 1.
Study Visit Definition for Psoriasis Symptoms 
Scale (PSS)
Psoriasis Symptoms Scale (PSS) is collected as a daily diary, entries will be mapped to study 
week by the following:
Weeka
Start Dayb
End Day
Baseline
Date of First Injectionc - 7
Date of First Injection-1
Week 1
Max(Date of First Injection, Week 2 Assessment Date – 14) 
Week 2 Assessment Date - 8
Week 2
Max(Baseline Assessment Date, Week 2 Assessment Date – 7) 
Week 2 Assessment Date - 1 
Week 3
Max(Week 2 Assessment Date, Week 4 Assessment Date – 14)
Week 4 Assessment Date -8
Week 4
Max(Week 2 Assessment Date, Week 4 Assessment Date – 7) 
Week 4 Assessment Date – 1
Week 5
Max(Week 4 Assessment Date, Week 8 Assessment Date – 28) 
Week 8 Assessment Date -22
Week 6
Max(Week 4 Assessment Date, Week 8 Assessment Date – 21)
Week 8 Assessment Date -15
Week 7
Max(Week 4 Assessment Date, Week 8 Assessment Date – 14) 
Week 8 Assessment Date -8
Week 8
Max(Week 4 Assessment Date, Week 8 Assessment Date – 7)
Week 8 Assessment Date – 1
Week 9
Max(Week 8 Assessment Date, Week 12 Assessment Date – 28) 
Week 12 Assessment Date -22
Week 10
Max(Week 8 Assessment Date, Week 12 Assessment Date – 21) 
Week 12 Assessment Date -15
Week 11
Max(Week 8 Assessment Date, Week 12 Assessment Date – 14) 
Week 12 Assessment Date -8
Week 12
Max(Week 8 Assessment Date, Week 12 Assessment Date – 7) 
Week 12 Assessment Date – 1
Week 13
Max(Week 12 Assessment Date, Week 16 Assessment Date – 28) 
Week 16 Assessment Date -22
Week 14
Max(Week 12 Assessment Date, Week 16 Assessment Date – 21) 
Week 16 Assessment Date -15
Week 15
Max(Week 12 Assessment Date, Week 16 Assessment Date – 14) 
Week 16 Assessment Date -8
Week 16
Max(Week 12 Assessment Date, Week 16 Assessment Date – 7) 
Week 16 Assessment Date – 1
a
If End Day < Start Day, do not assign specified visit week
b
Assessment Date is the date of the specified visit week’s PASI assessment. If the PASI assessment date is 
missing, the first date from the following order will be selected:  (1) date of dosing if injection was given, (2) 
office visit date if available, or (3) schedule date of visit from the protocol for that visit.
c
If date of first injection is missing, the randomization date will be used.
If multiple PSS assessments on a single day are present, use the latest assessment.  If more than 
7 days is available between assessment dates, use only the last 7 days as the range.  If the range 
contains at least 4 nonmissing daily assessments, calculate the average for the nonmissing daily 
assessments to get the weekly score.  If range contains fewer than 4 nonmissing daily 
assessments, then the weekly result is missing.


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Appendix 2.
Analysis Plan for Japan Addendum
App.2.1.
Japan Addendum Design and Objectives
The main protocol for Study I6T-MC-AMAJ (AMAJ) enrolls patients with plaque psoriasis 
(Cohort 1).  In parallel, the AMAJ(1) addendum will enroll Japanese patients who are diagnosed 
as generalized pustular psoriasis (GPP) by the Japanese Dermatological Association or 
erythrodermic psoriasis (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.
Eight patients with GPP and 8 patients with EP will be enrolled in Cohort 2 in Japan.  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).
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.  Table AMAJ.App.1 shows the addendum 
objectives and endpoints which are added to the study as exploratory objectives:


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Table AMAJ.App.1.
Japan Addendum 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; EP = erythrodermic 
psoriasis; PASI = Psoriasis Area and Severity Index.
* This endpoint is written as it is in Japan Addenda (1.1), but should be updated to “change from baseline in
assessment of dermal symptoms for GPP”.  
** This endpoint is written as it is in Japan Addenda (1.1), but should be updated to “global improvement score”.
App.2.2.
Japan Addendum General 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, health outcome, and safety analysis for plaque 
psoriasis, GPP, and EP will be conducted separately.  
The Japan Addendum Intent-to-Treat (ITT) Population – Patients with GPP or EP is defined as 
all GPP and EP patients who enrolled in the Japan addendum, even if the patient does not take 
the assigned treatment, does not receive the correct treatment, or otherwise does not follow the 
protocol.  All patients are assigned to mirikizumab treatment.  Efficacy/Health outcome analyses 
for the combined Induction and Maintenance Periods will be conducted on this population.  
Generalized pustular psoriasis and EP patients will be reported separately.


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The Japan Addendum Safety Population – Patients with GPP or EP is defined as all GPP and EP 
patients who enrolled in the Japan addendum and received at least 1 dose of study treatment.  
Safety analyses for the combined Induction and Maintenance Periods (which are similar to the 
All Active Treatment Periods for the 250-mg mirikizumab Q4W/250-mg mirikizumab Q8W in 
the main SAP) will be conducted on this population.  Generalized pustular psoriasis and EP 
patients will be reported separately.  
The definitions of the baselines for efficacy, health outcomes, and safety analyses in the Japan 
Addendum are the same as in the main protocol/SAP.
Due to small sample size in the Japan Addendum, no formal inferencial statistics will be 
performed.  Data will be summarized for GPP and EP patients separately.  The methods of 
summary are the same as in the main SAP
The following general summaries and/or listings will be provided based on Japan Addendum 
ITT Population – Patients with GPP or EP:

patient disposition including treatment disposition and study disposition

patient demographics and other baseline characteristics
o
Add baseline GPP dermal symptom total score

preexisting conditions

prespecified medical history

previous psoriasis therapy and the corresponding reason for discontinuation

prior medications and concomitant medications

study treatment exposure

listing of randomization/treatment assignment

important protocol deviations

treatment compliance
App.2.3.
Japan Addendum Efficacy/Health Outcome Analyses
Table AMAJ.App.3 includes the description and derivation of the additional efficacy measures 
and endpoints that are collected in the Japan Addendum
Table AMAJ.App.4 provides the detailed analyses for efficacy/health outcomes analyses in the 
Japan Addendum.


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Table AMAJ.App.3.
Description and Derivation of Additional Efficacy/Health Outcomes
Measures and Endpoints for Japan Addendum
Measure
Description
Variable
Derivation/Comment
Imputation 
Approach if 
with Missing 
Components
Global 
Improvement 
Score

Collected for patients with GPP 
or EP from Week 2.  

Assessed in the 4 grades by 
comparing the psoriatic findings:  
(1) resolved, (2) improved, (3) 
unchanged, (4) worsened.  

Assessed based on the 
comparison of the psoriatic 
findings, sPGA, PASI score, and 
other evaluations with those at 
the baseline.  
Global 
improvement 
score
As collected
Single item, 
missing if 
missing
Assessment 
of dermal 
symptoms

According to the Japanese 
Dermatological Association GPP 
revised criteria.a

Performed only for patients with 
GPP. 

Skin symptoms are assessed by 
the score with the area of 
erythema (on a 0-3 scale), the 
area of erythema with pustules 
(on a 0-3 scale), and the area of 
skin edema (on a 0-3), where 
0 = none; 1 = mild; 
2 = moderate; 3 = severe.
GPP dermal 
symptom 
total score
Sum of scores of the 
area of erythema, the 
area of erythema with 
pustules, and the area 
of skin edema.  Range 
from 0-9.  
If any 
individual 
score is 
missing, the 
total score 
will not be 
calculated, 
hence 
missing
Abbreviations:  EP = = erythrodermic psoriasis; GPP = generalized pustular psoriasis; PASI = Psoriasis Area and 
Severity Index; sPGA = static Physician’s Global Assessment.
a
(Terui et al. [WWW]).


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Table AMAJ.App.4.
Description of Efficacy/Health Outcomes Analyses for Japan 
Addendum
Measure
Variable
Analysis Method
Population
Time Point and 
Period
Global 
Improvement 
Score
Global improvement 
score
Descriptive statistics 
for each grade based 
on observed
Japan Addendum Intent-
to-Treat Population –
Patients with GPP or EP
All scheduled visits 
in Induction and 
Maintenance 
Periods
GPP dermal 
symptom 
total score
GPP dermal 
symptom total score 
change from baseline
Descriptive statistics 
based on observed 
and mBOCF
Japan Addendum Intent-
to-Treat Population –
Patients with GPP
All scheduled visits 
in Induction and 
Maintenance 
Periods
PASI
PASI change from 
baseline
Descriptive statistics 
based on observed 
and mBOCF
Japan Addendum Intent-
to-Treat Population –
Patients with GPP or EP
All scheduled visits 
in Induction and 
Maintenance 
Periods
DLQI
DLQI total score 
change from baseline
Descriptive statistics 
based on observed 
and mBOCF
Japan Addendum Intent-
to-Treat Population –
Patients with GPP or EP 
All scheduled visits 
in Induction and 
Maintenance 
Periods
Abbreviations:  DLQI = Dermatology Life Quality Index; EP = erythrodermic psoriasis; GPP = generalized pustular 
psoriasis; mBOCF = modified baseline observation carried forward; PASI = Psoriasis Area and Severity Index.
App.2.4.
Japan Addendum Safety Analyses
The following safety summaries will be provided for the Japan Addendum Safety Population –
Patients with GPP or EP, for the Induction and Maintenance Periods:

overview of adverse events (AEs)

treatment-emergent adverse event (TEAE) by Preferred Terms (PTs)

TEAE by PTs within System Organ Class

TEAE maximum severity by PTs 

serious adverse event (SAE) by PTs

AEs leading to treatment discontinuation

listings of SAEs

laboratory tests: box plot of change from baseline by visit

vital signs:  box plot of change from baseline by visit

immunogenicity: incidence of antidrug antibodies


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References
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.
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). Japanese Dermatological Association web site. 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.


Leo Document ID = c15f678f-bc2f-477e-97e6-dac29bfb1635
Approver: 
Approval Date & Time: 25-Nov-2019 17:34:55 GMT
Signature meaning: Approved
PPD