The purpose of this protocol is to evaluate the efficacy (how well it works), safety and
tolerability of oral icotrokinra as therapy in adult and adolescent participants with
moderately to severely active ulcerative colitis (UC, a chronic disease of the large
intestine in which the lining of the colon becomes inflamed and develops tiny open
ulcers).

A Protocol of Icotrokinra Therapy in Adult and Adolescent Participants With Moderately to Severely Active Ulcerative Colitis

Colitis, Ulcerative

Ulcerative Colitis

Gastrointestinal diseases

Immune system conditions

Placebo

Icotrokinra

A Phase 3 Randomized, Double-blind, Placebo-Controlled, Parallel Group, Multicenter Protocol in Adults With an Open Label Study in Adolescents to Evaluate the Efficacy and Safety of Induction and Maintenance Therapy With Icotrokinra in Participants With Moderately to Severely Active Ulcerative Colitis

Percentage of adult participants in clinical remission at Week I-12 will be reported.
Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal bleeding
subscore of 0, and an endoscopy subscore of 0 or 1.

Percentage of adult participants in clinical remission at Week M-40 will be reported.
Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal bleeding
subscore of 0, and an endoscopy subscore of 0 or 1.

Percentage of adolescent participants in clinical remission at Week M-40 will be
reported. Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal
bleeding subscore of 0, and an endoscopy subscore of 0 or 1.

Percentage of adult participants in clinical response at Week I-12 will be reported.
Clinical response is defined as a decrease from baseline in the modified Mayo score by
greater than or equal to (>=) 30 percent (%) and >=2 points, with either a >=1-point
decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0
or 1.

Percentage of adult participants with endoscopic improvement at Week I-12 will be
reported. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1.

Percentage of adult participants in symptomatic remission at Week I-12 will be reported.
Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal
bleeding subscore of 0.

Percentage of adult participants with IBDQ remission at Week I-12 will be reported. IBDQ
remission is defined as an IBDQ total score of >= 170. The IBDQ is a validated, 32-item,
self-reported questionnaire for participants with IBD that will be used to evaluate the
disease-specific health related quality of life (HRQoL) across 4 dimensional scores:
bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep
pattern), social function (work attendance, need to cancel social events), and emotional
function (anger, depression, irritability). Scores range from 32 to 224, with higher
scores indicating better outcomes.

Percentage of adult participants with HEMI at Week I-12 will be reported. HEMI is defined
as achieving a combination of histologic improvement and endoscopic improvement.
Histologic improvement is defined as neutrophil infiltration in less than (<) 5% of
crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue
according to the Geboes grading system. Endoscopic improvement is defined as an endoscopy
sub-score of 0 or 1.

Percentage of adult participants with fatigue response at Week I-12 will be reported.
Fatigue response is defined as a >= 7-point reduction in the patient-reported outcomes
measurement information system (PROMIS)-fatigue Short Form (SF)-7a total score from
baseline. The PROMIS fatigue SF-7a contains 7 items evaluating fatigue-related symptoms
(that is, tiredness, exhaustion, mental tiredness, and lack of energy) and associated
impacts on daily activities (that is, activity limitations related to work, self-care,
and exercise).

Percentage of adult participants in symptomatic remission at Week I-4 will be reported.
Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal
bleeding subscore of 0.

Percentage of adult participants in endoscopic remission at Week I-12 will be reported.
Endoscopic remission is defined as an endoscopy subscore of 0.

Percentage of adult participants with no bowel urgency at Week I-12 will be reported
using the ulcerative colitis patient-reported outcomes signs and symptoms (UC-PRO/SS).
The UC-PRO/SS is a 9-item measure that was developed to standardize the quantification of
gastrointestinal (GI) signs and symptoms of UC through direct report from participant
ratings. The module includes both bowel signs and symptoms and abdominal symptoms, with a
recall period of 24 hours.

Percentage of adult participants with no abdominal pain at Week I-12 will be reported
using the UC-PRO/SS. The UC-PRO/SS is a 9-item measure that was developed to standardize
the quantification of GI signs and symptoms of UC through direct report from participant
ratings. The module includes both bowel signs and symptoms and abdominal symptoms, with a
recall period of 24 hours.

Percentage of adult participants with no bowel incontinence at Week I-12 will be reported
using the UC-PRO/SS. The UC-PRO/SS is a 9-item measure that was developed to standardize
the quantification of GI signs and symptoms of UC through direct report from participant
ratings. The module includes both bowel signs and symptoms and abdominal symptoms, with a
recall period of 24 hours.

Percentage of adult participants with AEs and SAEs will be reported. An AE is any
untoward medical occurrence in a clinical study participant administered a pharmaceutical
(investigational or non-investigational) product that does not necessarily have a causal
relationship with the intervention. A SAE is any untoward medical occurrence that at any
dose results in death, is life-threatening, requires inpatient hospitalization or
prolongation of existing hospitalization, results in persistent or significant
disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission
of any infectious agent via a medicinal product, is medically important.

Percentage of adult participants with endoscopic improvement at Week M-40 will be
reported. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1.

Percentage of adult participants in symptomatic remission at Week M-40 will be reported.
Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a rectal
bleeding subscore of 0.

Percentage of adult participants with 90-day corticosteroid-free clinical remission at
Week M-40 will be reported. 90-day corticosteroid-free clinical remission is defined as
the clinical remission at the visit and not receiving corticosteroids for 90 days prior
to the visit.

Percentage of adult participants with HEMI at Week M-40 will be reported. HEMI is defined
as achieving a combination of histologic improvement and endoscopic improvement.
Histologic improvement is defined as neutrophil infiltration in < 5% of crypts, no crypt
destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes
grading system. Endoscopic improvement is defined as an endoscopy sub-score of 0 or 1.

Percentage of adult participants with IBDQ remission at Week M-40 will be reported. IBDQ
remission is defined as an IBDQ total score of >= 170. The IBDQ is a validated, 32-item,
self-reported questionnaire for participants with IBD that will be used to evaluate the
disease-specific HRQoL across 4 dimensional scores: bowel symptoms (loose stools,
abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function
(work attendance, need to cancel social events), and emotional function (anger,
depression, irritability). Scores range from 32 to 224, with higher scores indicating
better outcomes.

Percentage of adult participants in endoscopic remission at Week M-40 will be reported.
Endoscopic remission is defined as an endoscopy subscore of 0.

Percentage of adult participants in clinical remission at Week M-40 among the
participants who had achieved clinical remission at maintenance baseline will be
reported. Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal
bleeding subscore of 0, and an endoscopy subscore of 0 or 1.

Percentage of adult participants in histologic-endoscopic mucosal remission at Week M-40
will be reported. Histologic-endoscopic mucosal remission is defined as achieving a
combination of histologic remission and endoscopic remission. Histologic remission is
defined as the absence of neutrophils from the mucosa (both lamina propria and
epithelium), no crypt destruction, and no erosions, ulcerations or granulation tissue
according to the Geboes grading system. Endoscopic remission is defined as an endoscopy
subscore of 0.

Percentage of adult participants with fatigue response at Week M-40 will be reported.
Fatigue response is defined as a >= 7-point reduction in the PROMIS-fatigue SF-7a total
score from baseline. The PROMIS fatigue SF-7a contains 7 items evaluating fatigue-related
symptoms (that is, tiredness, exhaustion, mental tiredness, and lack of energy) and
associated impacts on daily activities (that is, activity limitations related to work,
self-care, and exercise).

Percentage of adult participants with disease clearance at Week M-40 will be reported.
Disease clearance is defined as a composite of symptomatic remission and
histologic-endoscopic mucosal remission. Symptomatic remission is defined as a stool
frequency subscore of 0 or 1 and a rectal bleeding subscore of 0. Histologic-endoscopic
mucosal remission is defined as achieving a combination of histologic remission and
endoscopic remission.

Percentage of adult participants with no bowel urgency at Week M-40 will be reported
using the UC-PRO/SS. The UC-PRO/SS is a 9-item measure that was developed to standardize
the quantification of GI signs and symptoms of UC through direct report from participant
ratings. The module includes both bowel signs and symptoms and abdominal symptoms, with a
recall period of 24 hours.

Percentage of adult participants with no abdominal pain at Week M-40 will be reported
using the UC-PRO/SS. The UC-PRO/SS is a 9-item measure that was developed to standardize
the quantification of GI signs and symptoms of UC through direct report from participant
ratings. The module includes both bowel signs and symptoms and abdominal symptoms, with a
recall period of 24 hours.

Percentage of adult participants with no bowel incontinence at Week M-40 will be reported
using the UC-PRO/SS. The UC-PRO/SS is a 9-item measure that was developed to standardize
the quantification of GI signs and symptoms of UC through direct report from participant
ratings. The module includes both bowel signs and symptoms and abdominal symptoms, with a
recall period of 24 hours.

Percentage of adult participants with AEs and SAEs will be reported. An AE is any
untoward medical occurrence in a clinical study participant administered a pharmaceutical
(investigational or non-investigational) product that does not necessarily have a causal
relationship with the intervention. A SAE is any untoward medical occurrence that at any
dose results in death, is life-threatening, requires inpatient hospitalization or
prolongation of existing hospitalization, results in persistent or significant
disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission
of any infectious agent via a medicinal product, and is medically important.

Percentage of adolescent participants in clinical response at Week I-12 will be reported.
Clinical response is defined as a decrease from baseline in the modified Mayo score by
greater than or equal to (>=) 30 percent (%) and >=2 points, with either a >=1-point
decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0
or 1.

Percentage of adolescent participants in clinical remission at Week I-12 will be
reported. Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal
bleeding subscore of 0, and an endoscopy subscore of 0 or 1.

Percentage of adolescent participants with HEMI at Week I-12 will be reported. HEMI is
defined as achieving a combination of histologic improvement and endoscopic improvement.
Histologic improvement is defined as neutrophil infiltration in less than (<) 5% of
crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue
according to the Geboes grading system. Endoscopic improvement is defined as an endoscopy
sub-score of 0 or 1.

Percentage of adolescent participants with endoscopic improvement at Week I-12 will be
reported. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1.

Percentage of adolescent participants in symptomatic remission at Week I-12 will be
reported. Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a
rectal bleeding subscore of 0.

Percentage of adolescent participants in endoscopic remission at Week I-12 will be
reported. Endoscopic remission is defined as an endoscopy subscore of 0.

Percentage of adolescent participants in PUCAI remission at Week I-12 will be reported.
PUCAI remission is defined as a PUCAI score <10. The PUCAI is a non-invasive instrument
for measuring disease activity in adolescents with UC. Disease activity is determined as
a score based on evaluation of abdominal pain, rectal bleeding, stool consistency, number
of stools, nocturnal bowel movement, and activity level. The PUCAI score ranges from 0 to
85.

Percentage of adolescent participants with AEs and SAEs will be reported. An AE is any
untoward medical occurrence in a clinical study participant administered a pharmaceutical
(investigational or non-investigational) product that does not necessarily have a causal
relationship with the intervention. A SAE is any untoward medical occurrence that at any
dose results in death, is life-threatening, requires inpatient hospitalization or
prolongation of existing hospitalization, results in persistent or significant
disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission
of any infectious agent via a medicinal product, and is medically important.

Percentage of adolescent participants with endoscopic improvement at Week M-40 will be
reported. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1.

Percentage of adolescent participants in symptomatic remission at Week M-40 will be
reported. Symptomatic remission is defined as a stool frequency subscore of 0 or 1 and a
rectal bleeding subscore of 0.

Percentage of adolescent participants in 90-day corticosteroid-free clinical remission at
Week M-40 will be reported. 90-day corticosteroid-free clinical remission is defined as
the clinical remission at the visit and not receiving corticosteroids for 90 days prior
to the visit.

Percentage of adolescent participants with HEMI at Week M-40 will be reported. HEMI is
defined as achieving a combination of histologic improvement and endoscopic improvement.
Histologic improvement is defined as neutrophil infiltration in < 5% of crypts, no crypt
destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes
grading system. Endoscopic improvement is defined as an endoscopy sub-score of 0 or 1.

Percentage of adolescent participants with histologic-endoscopic mucosal remission at
Week M-40 will be reported. Histologic-endoscopic mucosal remission is defined as
achieving a combination of histologic remission and endoscopic remission. Histologic
remission is defined as the absence of neutrophils from the mucosa (both lamina propria
and epithelium), no crypt destruction, and no erosions, ulcerations or granulation tissue
according to the Geboes grading system. Endoscopic remission is defined as an endoscopy
subscore of 0.

Percentage of adolescent participants with endoscopic remission at Week M-40 will be
reported. Endoscopic remission is defined as an endoscopy subscore of 0.

Percentage of adolescent participants in clinical remission at Week M-40 among the
participants who had achieved clinical remission at maintenance baseline will be
reported. Clinical remission is defined as stool frequency subscore of 0 or 1, a rectal
bleeding subscore of 0, and an endoscopy subscore of 0 or 1.

Percentage of adolescent participants in clinical response at Week M-40 among the
participants who had achieved clinical response at maintenance baseline will be reported.
Clinical response is defined as a decrease from baseline in the modified Mayo score by >=
30 % and >=2 points, with either a >=1-point decrease from baseline in the rectal
bleeding subscore or a rectal bleeding subscore of 0 or 1.

Percentage of adolescent participants in PUCAI remission at Week M-40 will be reported.
PUCAI remission is defined as a PUCAI score <10. The PUCAI is a non-invasive instrument
for measuring disease activity in adolescents with UC. Disease activity is determined as
a score based on evaluation of abdominal pain, rectal bleeding, stool consistency, number
of stools, nocturnal bowel movement, and activity level. The PUCAI score ranges from 0 to
85.

Adult participants will be randomized to receive icotrokinra daily, orally starting at
induction Week 0 (Week I-0). At Week I-12, all participants will be evaluated for
clinical response and will enter the Maintenance study.

Adult participants will be randomized to receive placebo daily, orally starting at Week
I-0. At Week I-12, all participants will be evaluated for clinical response and will
enter the Maintenance study.

Adult participants who are in clinical response to icotrokinra at the end of the
Induction study will enter the Maintenance study and be randomized to receive icotrokinra
daily, orally starting at maintenance Week 0 (Week M-0) through Week M-40. Participants
who are clinical nonresponders to icotrokinra or placebo will also enter the Maintenance
study directly and receive icotrokinra daily. After completion of the Maintenance study
through Week M-40, eligible participants can participate in a long-term extension (LTE).

Adult participants who are in clinical response to icotrokinra at the end of the
Induction study will enter the Maintenance study and be randomized to receive placebo
daily, orally starting at Week M-0 through Week M-40. Participants who are clinical
responders to placebo will also enter the Maintenance study directly and continue to
receive placebo daily. After completion of the Maintenance study through Week M-40,
eligible participants can participate in a LTE.

Adolescent participants will enter the Induction phase and receive icotrokinra daily,
orally. At Week I-12 all participants will be evaluated for clinical response and will
enter the Maintenance phase.

Adolescent participants who are in clinical response to icotrokinra will enter the
Maintenance phase at Week M-0 and continue to receive icotrokinra daily, orally up to
Week M-40. Participants who are nonresponders to icotrokinra will also enter the
Maintenance phase to receive icotrokinra daily. After completion of the Maintenance phase
through Week M-40, eligible participants can participate in a LTE.

Gastro Intestinal Research Institute of Northern Ohio LLC

University Gastroenterology

Tyler Research Institute, LLC

Gastroenterology Associates of Tidewater

Southern California Research Center

CIPREC

Gastromedic, Ltd.

CHU de Limoges Hopital Dupuytren

Clinfan Ltd. SMO

Asan Medical Center

CHU de Bordeaux - Hospital Haut-Leveque

Bnai Zion Medical Center

Rabin Medical Center

Hospital Ampang

NZOZ Centrum Medyczne KERmed

Centrum Medyczne Promed

Clinical Best Solutions Warszawa

Uls Alto Ave - Hosp. Sra. Da Oliveira Guimaraes

Kyung Hee University Hospital

Ankara Bilkent Sehir Hastanesi

Medical Associates Research Group, Inc.

New York Gastroenterology Associates

A Protocol of Icotrokinra Therapy in Adult and Adolescent Participants With Moderately to Severely Active Ulcerative Colitis

Trials at a glance

Trials at a glance

Eligibility criteria