The purpose of this study is to evaluate how-well icotrokinra works (clinical efficacy)
and how safe it is (safety) in participants with moderately to severely active Crohn's
disease (CD; a long-term condition causing severe inflammation of the intestinal tract).

A Study of Icotrokinra in Participants With Moderately to Severely Active Crohn's Disease

Crohn Disease

Crohn's Disease

Crohns Disease

Fistulizing Crohns Disease

Perianal Crohns Disease

Gastrointestinal diseases

Immune system conditions

Placebo

Icotrokinra

A Phase 2b/3 Randomized, Double-blind, Placebo-Controlled, Parallel Group, Multicenter Protocol to Evaluate the Efficacy and Safety of Icotrokinra in Participants With Moderately to Severely Active Crohn's Disease

Clinical response is defined as a greater than or equal to (>=) 100-point reduction from
baseline in Crohn's Disease Activity Index (CDAI) score. CDAI scores range from 0 to
approximately 600. Higher score indicates higher disease activity.

Clinical remission is defined as CDAI score less than (<) 150. CDAI scores range from 0
to approximately 600. Higher score indicates higher disease activity.

Endoscopic response is defined as greater than (>) 50% improvement from baseline in
Simple Endoscopic Score for Crohn's Disease (SES-CD) score or a decrease of at least 2
points in participants with a baseline score of 4 and isolated ileal disease. SES-CD
score can range from 0 to 56. Higher scores indicating more severe disease.

Clinical remission is defined as CDAI score < 150. CDAI scores range from 0 to
approximately 600. Higher score indicates higher disease activity.

Endoscopic response is defined as > 50% improvement from baseline in SES-CD score or a
decrease of at least 2 points in participants with a baseline score of 4 and isolated
ileal disease. SES-CD score can range from 0 to 56. Higher scores indicating more severe
disease.

Clinical remission is defined as CDAI score < 150. CDAI scores ranging from 0 to
approximately 600. Higher score indicates higher disease activity.

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. An 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.

PRO-2 remission is defined as an abdominal pain (AP) mean daily score less than or equal
to (<=) 1 and stool frequency (SF) mean daily score <= 2.8, and no worsening of AP or SF
from baseline.

Clinical response is defined as a >= 100-point reduction from baseline in CDAI score.

Clinical remission is defined as CDAI score < 150. Endoscopic response is defined as >
50% improvement from baseline in SES-CD score or a decrease of at least 2 points in
participants with a baseline score of 4 and isolated ileal disease. This is a composite
endpoint defined to measure achievement of both clinical remission and endoscopic
response at the participant level.

Endoscopic remission is defined as SES-CD <= 4 with at least a 2-point reduction from
baseline and no sub score >1 in any individual component.

Deep remission is a composite endpoint defined as achieving both clinical remission and
endoscopic remission at the participant level. Clinical remission is defined as CDAI
score < 150-point. Endoscopic remission is defined as SES-CD <= 4 with at least a 2-point
reduction from baseline and no sub score >1 in any individual component.

IBDQ remission is defined as IBDQ score >= 170. IBDQ is a validated, 32-item,
self-reported questionnaire for participants with inflammatory bowel disease (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.

Fatigue response is defined as a >= 7 point reduction in the patient reported outcomes
measurement information system (PROMIS)-Fatigue Short Form 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). Item responses are rated on a five-point scale ranging from "never" to
"always". Higher scores indicate more fatigue.

Clinical remission is defined as CDAI score< 150.

Histologic remission is defined as a Robarts Histopathology Index score <=3, where each
of the items of lamina propria neutrophils, neutrophils in epithelium, and erosions or
ulcerations must be equal to 0. Endoscopic remission is defined as SES-CD <= 4 with at
least a 2-point reduction from baseline and no sub score >1 in any individual component.
This is a composite endpoint defined as achieving both histologic remission and
endoscopic remission at the participant level.

PRO-2 remission is defined as an abdominal pain (AP) mean daily score <= 1 and stool
frequency (SF) mean daily score <= 2.8, and no worsening of AP or SF from baseline.

90-day corticosteroid-free clinical remission is defined as the clinical remission at the
visit and not receiving corticosteroids for at least 90 days prior to the visit. Clinical
remission is defined as CDAI score < 150.

Participants with clinical remission at Week 40 among those with clinical remission at
Week 0 of the maintenance study will be analyzed. Clinical remission is defined as CDAI
score < 150.

Deep remission is a composite endpoint defined as achieving both clinical remission and
endoscopic remission at the participant level. Clinical remission is defined as CDAI
score < 150. Endoscopic remission is defined as SES-CD <= 4 with at least a 2-point
reduction from baseline and no sub score >1 in any individual component.

IBDQ remission is defined as IBDQ score >= 170. 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.

Fatigue response is defined as a >= 7 point reduction in the PROMIS-Fatigue Short Form 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). Item responses are rated on a five-point scale ranging
from "never" to "always". Higher scores indicate more fatigue.

Participants will receive Icotrokinra dose 1 in Induction Study 1 up to Week 12.
Subsequent treatment will be determined by the participant's response status at Week 12.

Participants will receive Icotrokinra dose 2 in Induction Study 1 up to Week 12.
Subsequent treatment will be determined by the participant's response status at Week 12.

Participants will receive matching placebo in Induction Study 1 up to Week 12. Subsequent
treatment will be determined by the participant's response status at Week 12.

Participants will receive Icotrokinra at the dose regimen determined in Induction Study 1
up to Week 12. Subsequent study treatment will be determined by the participant's
response status at Week 12.

Participants will receive matching placebo for up to Week 12. Subsequent study treatment
will be determined by the participant's response status at Week 12.

Participants who were receiving icotrokinra in either induction studies 1 or 2 and were
in response at Week 12 of the induction study will be randomized to receive icotrokinra
maintenance dose 1. Participants receiving Icotrokinra Dose 1 and meeting criteria for
loss of response during the Maintenance Study will be eligibile for a single blinded dose
adjustment to Icotrokinra Dose 2. After completion of the Maintenance Study through Week
40, eligible participants can participate in long-term extension (LTE).

Participants who were receiving icotrokinra in either induction studies 1 or 2 and were
in response at Week 12 of the induction study will be randomized to receive icotrokinra
maintenance dose 2. Participants who were non-responders at Week 12 of the induction
studies will also receive icotrokinra maintenance dose 2 but will not be randomized.
After completion of the Maintenance Study through Week 40, eligible participants can
participate in LTE.

Participants who were receiving icotrokinra in either induction studies 1 or 2 and were
in response at Week 12 will be randomized to receive placebo. Participants receiving
placebo in induction studies 1 or 2 and in response at Week 12 of the induction study
will continue to receive placebo during maintenance on non-randomized basis. Placebo
non-responders from induction study will receive icotrokinra maintenance dose 2 on a
non-randomized basis and will be assessed for response at Week 12.

Participants receiving placebo and meeting criteria for loss of response during the
Maintenance Study will be eligible for a single blinded dose adjustment to icotrokinra
dose 2. After completion of the Maintenance Study through Week 40, eligible participants
can participate in LTE.

Gastro Intestinal Research Institute of Northern Ohio LLC

University Gastroenterology

Tyler Research Institute, LLC

Gastroenterology Associates of Tidewater

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. Clinical
remission is defined as CDAI score < 150.

Medical Associates Research Group, Inc.

Digestive Disease Associates

Ha'Emek Medical Center

A Study of Icotrokinra in Participants With Moderately to Severely Active Crohn's Disease

Trials at a glance

Trials at a glance

Eligibility criteria