Moderately to Severely Active Ulcerative Colitis

Primary objective To evaluate the long-term efficacy of mirikizumab in the following cohort: Cohort 1: Patients from AMBG who completed Week 40 visit on blinded SC mirikizumab Efficacy To evaluate the long-term efficacy of mirikizumab in the following cohort: Cohort 1: Patients from AMBG who completed Week 40 visit on blinded SC mirikizumab To evaluate the long-term efficacy of mirikizumab in the following groups of patients: Cohort 2: Cohort 1 and AMAC patients who completed the Maintenance Period Week 52 visit on SC mirikizumab Cohort 3: The remaining patients (those not in Cohort 2) To evaluate the effect of long term mirikizumab therapy on histologic remission (mucosal healing) in the following cohorts: Cohort 1: Patients from AMBG who completed Week 40 visit on blinded SC mirikizumab Cohort 2: Cohort 1 and AMAC patients who completed the maintenance period Week 52 visit on SC mirikizumab

Mirikizumab (LY3074828)

(LY3074828)

Syringe

100

Primary:
The proportion of patients in clinical remission at Week 52

Efficacy:
 The proportion of patients in clinical remission at Week
100 or Week 160
 The proportion of patients in endoscopic remission at
Week 52, Week 100, or Week 160
 The proportion of patients with endoscopic subscore = 0
(ES=0) at Week 52, Week 100, or Week 160
 Stool frequency and rectal bleeding subscores over time
 The proportion of patients in corticosteroid-free
remission at Week 52, Week 100, or Week 160
 Among patients entering the AMAP study not on
corticosteroids, the time to first use of corticosteroids for
UC
 Dose of corticosteroid used at Week 52, Week 100, or
Week 160
 The proportion of patients in clinical remission at Week
52, Week 100, or Week 160
 The proportion of patients in endoscopic remission at
Week 52, Week 100, or Week 160
 The proportion of patients with ES = 0 at Week 52,
Week 100, or Week 160
 Stool frequency and rectal bleeding subscores over time
 Among the patients who enter the AMAP study on
corticosteroids, the proportion in corticosteroid-free
remission at Week 52, Week 100, or Week 160
 The proportion of patients in histologic remission at
Week 52, Week 100, or Week 160, as defined in the
histopathology charter

Informed Consent
[1.] Have given written informed consent approved by the ethical review board
(ERB) governing the site prior to any study-specific procedures being
completed.
Type of Patient and Disease Characteristics
[2.] Patients from the Phase 2 Study AMAC who:
 completed either the maintenance dosing period Week 52 or extension
period maintenance Week 40 assessments including endoscopy, and
 in the opinion of the investigator, would derive benefit from treatment
with mirikizumab
Patients should receive first dose of AMAP study within approximately 4
weeks of last dosing visit AMAC. A maximum of 8 weeks will be allowed
between last dose in AMAC and first dose in AMAP.
[3.] Patients from the Phase 3 Study AMBG who:
 completed the:
o Week 40 visit on blinded SC therapy without experiencing loss of
response during Study AMBG or
o Week 40 visit on open-label SC mirikizumab after responding to
re-induction with IV mirikizumab or
o AMBG early termination visit after completing IV rescue for LOR
and
 in the opinion of the investigator, would derive benefit from treatment with
mirikizumab.
Patients should receive first dose of AMAP study on the day of the AMBG
Week 40 visit, or within approximately 4 weeks after Week 40; a maximum
of 8 weeks will be allowed between last dose in AMBG and first dose in
AMAP.
Patient Characteristics
[4.] are willing and able to complete the scheduled study assessments, including
endoscopy
[5.] Contraception
[5a] male patients:
No male contraception required except in compliance with specific
local government study requirements
[5b] female patients:
women of child-bearing potential:
A. must test negative for pregnancy prior to initiation of treatment as
indicated by a negative urine pregnancy test at V1/Week 0 of this study.
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, or
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 following completion of study
drug administration for 12 weeks.
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.
ii. Of note, 1 of the 2 methods of contraception may be a highly
effective (<1% failure rate) method of contraception (such as
combination oral contraceptives, implanted contraceptives, or
intrauterine devices).
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 either
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
b. at least 6 months 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.
[6.] have documentation of
[6a] a surveillance colonoscopy (performed according to local standard)
within 18 months before Week 0 for:
 patients with pancolitis of >8 years’ duration, or
 patients with left-sided colitis of >12 years’ duration, or
 patients with primary sclerosing cholangitis.
Patients who do not have documentation of a surveillance colonoscopy with
negative report within 18 months prior to Week 0 will require a colonoscopy
at Week 0 to ensure eligibility
[6b] in patients for whom inclusion criterion [4a] does not apply, up-to-date
screening for colorectal cancer, (performed according to local standard).

Type of Patient and Disease Characteristics
[7.] Would not, in the opinion of the investigator, derive clinical benefit from
open-label treatment with mirikizumab.
[8.] Participated in AMAC and did not complete Maintenance Dosing Period
Week 52 or Extension Period Maintenance Week 40 assessments including
endoscopy.
[9.] Participated in AMBG and did not benefit, in the opinion of the investigator,
from IV rescue for LOR, or did not achieve clinical response following
extended IV induction with mirikizumab.
[10.] Had a reported SAE in originator study or developed other condition prior to
Week 0 visit that would disqualify them from treatment with mirikizumab
according to originator study criteria.
[11.] Had permanently discontinued, or had temporary interruption of, study drug
in originator study such that, in the opinion of the investigator or Sponsor,
restarting of mirikizumab would pose an unacceptable risk for the patient’s
participation in Study AMAP.
Medical Conditions
[12.] Presence of significant uncontrolled neuropsychiatric disorder or judged at
risk of suicide in the opinion of the investigator;
OR
marked “yes” to Columbia-Suicide Severity Rating Scale (C-SSRS) Question
4 or 5 on ideation prior to dosing at Week 0;
OR
marked “yes” to C-SSRS suicide behaviors questions prior to dosing at
Week 0;
AND
the ideation or behavior occurred within the past month.
[13.] Have an unstable or uncontrolled illness, including, but not limited to,
cerebro-cardiovascular, respiratory, gastrointestinal (excluding UC), hepatic,
renal, endocrine, hematologic or neurological disorders, or abnormal
laboratory values that developed during a previous mirikizumab study that, in
the opinion of the investigator, would pose an unacceptable risk to the patient
if investigational product continues to be administered.
[14.] Are diagnosed with any medical condition (or signs or symptoms thereof)
including developing malignancy or suspicion of active malignant disease
during the originator study or prior to Week 0, which would have precluded
enrollment in a prior mirikizumab study or would have required
discontinuation. Patients who require colorectal cancer surveillance
colonoscopy to (see IC [6a] and Section 9.1.3) will need a colonoscopy
within 18 months of Week 0 or at Week 0 to ensure eligilibity.
[15.] Have been diagnosed with serious infection (including but not limited to
hepatitis B, hepatitis C, HIV, and active tuberculosis [TB]) during the
originator study or prior to Week 0.
[16.] Have been diagnosed with latent TB during an originator study or prior to
Week 0 and is not willing to comply with completing TB treatment as
appropriate.
[17.] Have a known hypersensitivity to any component of this investigational
product, or has experienced an acute systemic hypersensitivity event with
previous study drug administration, that precludes mirikizumab therapy.
[18.] Have any other condition that in the opinion of the investigator, renders the
patient unable to understand the nature, scope, and possible consequences of
the study or precludes the patient from attending study visits, completing
study procedures, or adhering to prohibited concomitant medication
requirements (Appendix 9).
General Exclusion Criteria
[19.] Are pregnant, lactating, or planning pregnancy (women only) while enrolled
in the study, or within 12 weeks after receiving the last dose of study drug.
[20.] Had surgical intervention for ulcerative colitis after participation in a
previous mirikizumab UC study or likely to require surgery for treatment of
UC during the study.
[21.] Intend to receive a Bacillus Calmette-Guerin (BCG) vaccination or live
attenuated vaccine(s) during the study.
[22.] Have current adenomatous polyps that have not been removed. Patient may
be eligible for study after polyps are removed and histopath report received.
Patients with dysplasia within a polyp (dysplasia-associated lesion or mass)
should have documentation of a follow-up colonoscopy without recurrence.
[23.] 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
[24.] Are a Lilly employee, employee of third party organizations involved with
the study, or investigator site personnel directly affiliated with this study
and/or their immediate families, during the originator study.