A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate
the Efficacy and Safety of Guselkumab Subcutaneous Induction Therapy in Participants With
Moderately to Severely Active Crohn's Disease

1. Man or woman (according to their reproductive organs and functions assigned
by chromosomal complement) of >=18 years of age (or the legal age of consent in
the jurisdiction in which the study is taking place).
2. Have Crohn*s disease or fistulizing Crohn*s disease of at least 3 months
duration (defined as a minimum of 12 weeks), with colitis, ileitis, or
ileocolitis, confirmed at any time in the past by radiography, histology,
and/or endoscopy.
3. Have clinically active Crohn*s disease, defined as a baseline CDAI score
>=220 but <=450 and either:
a. Mean daily SF count >=4, based on the unweighted CDAI component of the number
of liquid or very soft stools. OR
b. Mean daily AP score >=2, based on the unweighted CDAI component of AP CNTO
1959 (guselkumab)
4. Have endoscopic evidence of active ileocolonic Crohn*s disease as assessed
by central endoscopy reading at the screening endoscopy (SoA [Section 1.3])
defined as a screening SES-CD score >=6 (or >=4 for participants with isolated
ileal disease), based on the presence of ulceration in at least 1 of the 5
ileocolonic segments, resulting in the following specified ulceration component
scores:
a. A minimum score of 1 for the component of *size of ulcers* AND
b. A minimum score of 1 for the component of *ulcerated surface*
5. A participant who has had extensive colitis for >=8 years, or disease limited
to a segment of the colon for >=10 years, must:
a. Have had a full colonoscopy to assess for the presence of dysplasia within 1
year before the first dose of study intervention. OR
b. Has a full colonoscopy with biopsy surveillance for dysplasia as the
baseline endoscopy during the screening period. Results from these surveillance
biopsies must be negative for dysplasia (low-grade, high-grade, or *indefinite
dysplasia in reactive atypia*) prior to the first dose of study intervention.

Concomitant or Previous Medical Therapies Received
6. Prior or current medication for Crohn*s disease must include at least 1 of
the following, and must fulfill additional criteria as described in Appendix 2
(Section 10.2) and Appendix 3 (Section 10.3)as applicable:
a. Current treatment with oral corticosteroids (including budesonide and
beclomethasone dipropionate) and/or immunomodulators (AZA, 6-MP, MTX) OR
b. History of failure to respond to, or tolerate, at least 1 of the following
therapies: oral corticosteroids (including budesonide and beclomethasone
dipropionate) or immunomodulators (AZA, 6-MP, MTX) OR
c. History of corticosteroid dependence (ie, an inability to successfully taper
corticosteroids without a return of the symptoms of Crohn*s disease) OR
d. Has previously demonstrated lack of initial response (ie, primary
nonresponders), responded initially but then lost response with continued
therapy (ie, secondary nonresponders), or were intolerant to 1 or more biologic
agents at a dose that is, at minimum, a locally approved dose for the treatment
of Crohn's disease (ie, infliximab, adalimumab, certolizumab pegol,
vedolizumab, or approved biosimilars for these agents)
Note: Participants meeting criteria 6a-c may either be naïve to biologic
therapy (ie, infliximab, adalimumab, certolizumab pegol, vedolizumab, or
approved biosimilars for these agents) or may have been exposed to these
biologic therapies and did not demonstrate an inadequate response or
intolerance.
7. Adhere to all of the following requirements for concomitant medication for
the treatment of Crohn*s disease. The following medications are permitted
provided that doses meeting the requirements listed below are stable or have
been discontinued prior to baseline within the timeframes specified below:
a. Oral 5-ASA compounds on stable doses for at least 2 weeks; or if recently
discontinued, must have been stopped for at least 2 weeks.
b. Oral corticosteroids at a prednisone-equivalent dose at or below 40 mg/day,
or 9 mg/day of budesonide, or 5 mg/day beclomethasone dipropionate, and on
stable dosing for at least 2 weeks; or if recently discontinued, must have been
stopped for at least 2 weeks.
c. Conventional immunomodulators (ie, AZA, 6-MP, or MTX) for at least 12 weeks
and have been on a stable dose for at least 4 weeks; or if recently
discontinued, must have been stopped for at least 4 weeks.
d. If receiving antibiotics as a primary treatment of Crohn*s disease, doses
must be stable for at least 3 weeks; or if recently discontinued, must have
been stopped for at least 3 weeks.
e. If receiving enteral nutrition as a primary treatment for Crohn*s disease,
must have been receiving for at least 2 weeks; or if recently discontinued,
must have been stopped for at least 2 weeks.

Screening Laboratory Tests
8. Have screening laboratory test results within the following parameters, and
if 1 or more of the laboratory parameters are out of range, a single retest of
laboratory values is permitted during the approximately 5-week screening period:
a. Hemoglobin >=8.0 g/dL
b. White blood cells (WBCs) >=3.0 x 10 exponent 3 /µL
c. Neutrophils >=1.5 x 10 exponent 3 /µL
d. Platelets >=100 x 10 exponent 3 /µL
e. Serum creatinine <=1.5 mg/dL
f. Alanine transaminase (ALT) (or aspartate transaminase [AST])<=2 x upper limit
of normal (ULN)
g. Total bilirubin (TBili) <=1.5 x ULN (Isolated total bilirubin >1.5 x ULN is
allowed for those participants with known Gilbert*s syndrome. Gilbert*s
syndrome is suggested by direct bilirubin <30% [Palmer 2020].)

Tuberculosis
9. A potential participant is considered eligible if the participant meets all
of the following TB screening criteria:
Note: Interferon gamma release assay (IGRA) testing includes either
QuantiFERON-TB® or T-SPOT® .TB.
a. Have no history of active TB or show signs or symptoms suggestive of active
TB upon medical history and/or physical examination at screening.
b. Have no history of latent TB prior to screening. An exception is made for
participants who have a history of latent TB AND who satisfy one of the
following criteria:
1) Currently receiving treatment for latent TB OR
2) Will initiate treatment for latent TB prior to the first administration of
study intervention
Note: For participants with a history of treated latent TB there must be
documentation of appropriate treatment prior to the first administration of
study intervention. It is the responsibility of the investigator to verify the
adequacy of previous TB treatment and provide appropriate documentation. IGRA
testing is not required at screening for participants with a history of treated
latent TB or ongoing treatment for latent TB.
c. Have had no recent close contact with a person with active TB. If there has
been contact, such participants are referred to a physician specializing in TB
to determine if treatment is warranted or not. This evaluation must be
adequately documented and, if treatment is recommended, the participant must be
receiving appropriate treatment prior to the first administration of study
intervention.
d. Have a negative IGRA test result within 2 months prior to the first
administration of study intervention, or who:
- Have a history of adequately treated latent TB described above.
- Have a newly identified positive IGRA test result in which active TB has been
ruled out and for which appropriate treatment for latent TB has been initiated
prior to the first administration of study intervention.
- Have a false-positive IGRA test as determined by the following: * A suspected
false-positive initial IGRA test must be repeated. If repeat testing is NOT
positive, the participant must be referred to a physician specializing in TB to
determine if the initial test can be considered a false-positive. This
evaluation must be adequately documented prior to the first administration of
study intervention. If repeat testing is positive, however, it will be
considered a true-positive and the participant is only eligible if active TB
has been ruled out and appropriate treatment for latent TB has been initiated
as described
above.
e. Have a chest radiograph (both posterior-anterior and lateral views, or per
local/country regulations where applicable), or chest computed tomography (CT)
within 3 months prior to the first administration of study intervention that
shows no abnormalities suggestive of active or inactive TB.

Contraception
10. A woman of childbearing potential must have a negative serum pregnancy test
result at screening.
11. Before randomization, a woman must be (as defined in Appendix 7 [Section
10.7])
a. Not of childbearing potential (refer to Section 10.7 for instances when a
screening follicle stimulating hormone (FSH)test should be considered) OR
b. Of childbearing potential and
o If heterosexually active, practicing a highly effective method of
contraception (failure rate of <1% per year when used consistently and
correctly)and agrees to remain on a highly effective method while receiving
study intervention and until 12 weeks after last dose -the end of relevant
systemic exposure. Note: The method selected must meet local/regional
regulations/guidelines for highly effective contraception. Note: If a
participant*s childbearing potential changes after start of the study (eg, a
premenarchal woman experiences menarche) or the risk of pregnancy changes (eg,
a woman who is not heterosexually active becomes active), a woman must begin
using a highly effective method of contraception.
12. A woman must agree not to donate eggs (ova, oocytes) for the purposes of
assisted reproduction during the study and for a period of 12 weeks after the
last administration of study intervention.
13. During the study and for at least 12 weeks after the last administration of
study intervention, a male participant:
a. Who is sexually active with a female of childbearing potential must agree to
use a barrier method of contraception (ie, condom with spermicidal
foam/gel/film/cream/suppository or female condom/occlusive cap [diaphragm or
cervical/vault caps] with spermicidal foal/gel/film/cream/suppository)
b. Who is sexually active with a pregnant female must use a condom
c. Must agree not to donate sperm for the purpose of reproduction

General
14. Each participant must sign an informed consent form (ICF) indicating that
he or she understands the purpose of, and procedures required for, the study
and is willing to participate in the study.
15. Must sign a separate ICF if he or she agrees to provide an optional DNA
sample for research (where local regulations permit). Refusal to give consent
for the optional DNA research sample does not exclude a participant from
participation in the study.
16. Be willing and able to adhere to all specified requirements, including but
not limited to completion of assessments, adherence to visit schedule, and
compliance with the lifestyle restrictions.

1. Has complications of Crohn*s disease, such as symptomatic strictures or
stenoses, short gut syndrome, or any other manifestation, that might be
anticipated to require surgery, could preclude the use of the CDAI to assess
response to therapy, or would possibly confound the ability to assess the
effect of treatment with guselkumab.
2. Currently has or is suspected to have an abscess. Recent cutaneous and
perianal abscesses are not exclusionary if drained and adequately treated at
least 3 weeks before baseline, or 8 weeks before baseline for intra-abdominal
abscesses, provided that there is no anticipated need for any further surgery.
Participants with active fistulas may be included if there is no anticipation
of a need for surgery and no abscesses are currently identified.
3. Has had any kind of bowel resection within 24 weeks, or any other
intra-abdominal or other major surgery within 12 weeks, before first dose of
study intervention.
4. Has a draining (ie, functioning) stoma or ostomy.
5. Presence on screening endoscopy of adenomatous colonic polyps, if not
removed before study entry, or history of adenomatous colonic polyps that were
not removed.
6. Has a stool culture or other examination positive for an enteric pathogen,
including Clostridioides difficile (formerly known as Clostridium difficile)
toxin, within 4 months before the first dose of study intervention, unless a
repeat examination is negative and there are no signs of ongoing infection with
that pathogen.

Concomitant or Previous Medical Therapies Received
7. Has received any of the following prescribed medications or therapies within
the specified period:
a. IV corticosteroids received within 3 weeks of baseline
b. Cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil received
within 8 weeks of baseline
c. 6-thioguanine received within 4 weeks of baseline
d. Biologic agents:
1) Anti-TNFα therapy (eg, infliximab, etanercept, certolizumab pegol,
adalimumab, golimumab) received within 8 weeks of baseline
2) Vedolizumab received within 12 weeks of baseline
3) Other immunomodulatory biologic agents, including approved and
investigational biologic agents, received within 12 weeks of baseline or within
5 half-lives of baseline, whichever is longer
e. Any investigational intervention received within 4 weeks of baseline or
within 5 half-lives of baseline, whichever is longer. (Refer to exclusion
criterion 7.d.3 for investigational biologic agents).
f. Non-autologous stem cell therapy (eg, Prochymal), natalizumab, efalizumab,
or biologic agents that deplete B- or T-cells (eg, rituximab, alemtuzumab, or
visilizumab) received within 12 months of baseline.
g. Treatment with apheresis (eg, Adacolumn apheresis) or total parenteral
nutrition for Crohn*s disease within 3 weeks of baseline.
8. Has previously received a biologic agent targeting IL-12/23 or IL-23,
including but not limited to ustekinumab, briakinumab, brazikumab, guselkumab,
mirikizumab, and risankizumab.

Infections or Predisposition to Infections:
9. Has a history of latent or active granulomatous infection, including
histoplasmosis or coccidioidomycosis, before screening. Participants with
radiographic evidence of possible prior histoplasmosis or coccidioidomycosis
will be excluded.
10. Has a history of, or ongoing, chronic or recurrent infectious disease,
including but not limited to, sinopulmonary infections, bronchiectasis,
recurrent renal/urinary tract infections (eg, pyelonephritis, cystitis), an
open, draining, or infected skin wound, or an ulcer.
11. Chest radiograph must be obtained within 12 weeks before the first dose of
study intervention. Results that shows an abnormality suggestive of an
undiagnosed pulmonary pathology including but not limited to a malignancy, a
previously unrecognized pulmonary pathology, as well as active or latent
infections from TB, histoplasmosis, or coccidiomycosis would be exclusionary. A
chest CT scan obtained outside of the protocol instead of a chest radiograph is
also acceptable. Refer to inclusion criteria 9 for information regarding
eligibility with a history of latent TB.
12. History of human immunodeficiency virus (HIV) antibody positive, or tests
positive for HIV at screening.
13. Is seropositive for antibodies to hepatitis C virus (HCV), unless they
satisfy one of the following conditions:
a. Has a history of successful treatment, defined as being negative for HCV RNA
at least 12 weeks after completing antiviral treatment, and has a negative HCV
RNA test result at screening, OR
b. While seropositive has a negative HCV RNA test result at least 12 weeks
prior to screening and a negative HCV RNA test result at screening.
14. Tests positive for hepatitis B virus (HBV) infection (Appendix 4[Section
10.4]).
15. Bacille Calmette-Guérin (BCG) vaccination within 12 months or any other
live bacterial or live viral vaccination within 4 weeks prior to screening, or
plans to receive such vaccines during the study.
16. Has or has had a nontuberculous mycobacterial infection or clinically
significant opportunistic infection (eg, cytomegalovirus colitis,
pneumocystosis, invasive aspergillosis).
17. Has had a clinically significant infection (ie, hepatitis, sepsis,
pneumonia, or pyelonephritis), has been hospitalized for an infection, or has
been treated with parenteral antibiotics for an infection within 8 weeks before
the first dose of study intervention. Treated and resolved infections not
considered clinically significant at the discretion of the investigator need
not be exclusionary (ie, acute upper respiratory tract infection, uncomplicated
urinary tract infection).
18. Has current signs or symptoms of a clinically significant infection.
Ongoing infections not considered clinically significant at the discretion of
the investigator need not be exclusionary (ie, acute upper respiratory tract
infection, uncomplicated urinary tract infection).
19. Has evidence of a herpes zoster infection within 8 weeks before the first
dose of study intervention.
20. During the 6 weeks prior to baseline, have had ANY of (a) confirmed severe
acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (Coronavirus Disease 2019
[COVID-19]) infection (test positive), OR (b) suspected SARS-CoV-2 infection
(clinical features without documented test results), OR (c) close contact with
a person with known or suspected SARS-CoV-2 infection Exception: May be
included with a documented negative result for a validated SARS-CoV-2 test
a. Obtained at least 2 weeks after conditions (a), (b), (c) above (timed from
resolution of key clinical features ifpresent, eg, fever, cough, dyspnea) AND
b. With absence of ALL conditions (a), (b), (c) above during the period between
the negative test result and the baseline study visit
Note on COVID-19-related exclusion:
* The field of COVID-19-related testing (for presence of, and immunity to, the
SARS-CoV-2 virus) is rapidly evolving. Additional testing may be performed as
part of screening and/or during the study if deemed necessary by the
investigator and in accordance with current regulations/guidance from
authorities/standards of care.
* Precaution: for those who may carry a higher risk for severe COVID-19
illness, follow guidance from local health authorities when weighing the
potential benefits and risks of enrolling in the study, and during
participation in the study.

Malignancy or Increased Potential for Malignancy:
21. Currently has a malignancy or has a history of malignancy within 5 years
before screening (with the exception of a nonmelanoma skin cancer that has been
adequately treated with no evidence of recurrence for at least 3 months
[defined as a minimum of 12 weeks] before the first dose of study intervention
or cervical carcinoma in situ that has been treated with no evidence of
recurrence for at least 3 months before the first dose of study intervention).
22. Has a known history of lymphoproliferative disease, including lymphoma, a
history of monoclonal gammopathy of undetermined significance; or signs and
symptoms suggestive of possible lymphoproliferative disease, such as
lymphadenopathy or splenomegaly.

Coexisting Medical Conditions or Past Medical History
23. Has a history of severe, progressive, or uncontrolled renal, genitourinary,
hematologic, endocrine, cardiac, vascular, pulmonary, rheumatologic,
neurologic, psychiatric, or metabolic disturbances, or signs and symptoms
thereof.
24. Has a transplanted organ (with exception of a corneal transplant >12 weeks
before screening).
25. Poor tolerability of venipuncture or lacks adequate venous access for
required blood sample collections during the study period.
26. History of drug or alcohol abuse according to Diagnostic and Statistical
Manual of Disorders (5th edition) criteria within 1 year before screening.
27. Has unstable suicidal ideation or suicidal behavior in the last 6 months
that may be defined as a Columbia-Suicide Severity Rating Scale (C-SSRS) rating
at screening of: suicidal ideation with intention to act (*Ideation level 4*),
suicidal ideation with specific plan and intent (*Ideation level 5*), or
suicidal behavior (actual suicide attempt, interrupted suicide attempt, aborted
suicide attempt, or preparatory behaviors for making a suicide attempt), and is
considered to be at risk by the investigator based on an evaluation by a mental
health professional. In addition, participants with C-SSRS ratings of wish to
be dead (*Ideation level 1*), non-specific active suicidal thoughts (*Ideation
level 2*), active suicidal ideation with any methods (not plan) without intent
to act (*Ideation level 3*) or non-suicidal self-injurious behavior who are
determined to be at risk by the investigator may not be randomized.
28. Has known allergy, hypersensitivity, or intolerance to guselkumab or its
excipients (refer to the guselkumab IB).
29. Is a woman who is pregnant, or breastfeeding, or planning to become
pregnant while enrolled in this study or within 12 weeks after the last dose of
study intervention.
30. Is a man who plans to father a child while enrolled in this study or within
12 weeks after the last dose of study intervention.

General
31. Currently participating or intends to participate in any other study using
an investigational agent or procedure during the conduct of this study.
32. Has any condition for which, in the opinion of the investigator,
participation would not be in the best interest of the participant (eg,
compromise the well-being) or that could prevent, limit, or confound the
protocol-specified assessments.
33. Is an employee of the investigator or study site, with direct involvement
in the proposed study or other studies under the direction of that investigator
or study site, as well as family members of the employees or the investigator.