A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Ustekinumab Induction Therapy in Subjects with Moderately to Severely Active Crohn*s Disease

1. Be a man or woman >= 18 years of age.;2. Have Crohn*s disease or fistulizing Crohn*s disease of at least 3 months* duration, with
colitis, ileitis, or ileocolitis, confirmed at any time in the past by radiography, histology,
and/or endoscopy. ;3. Have active Crohn*s disease, defined as:
a. A baseline CDAI score of * 220 and * 450,
AND
b. At least one of the following:
1) An abnormal CRP (> 0.3 mg/L) at screening;
OR
2) Calprotectin > 250 mg/kg at screening;
OR
3) Endoscopy with evidence of active Crohn*s disease during the current disease flare
(defined as ulcerations in the ileum and/or colon). The endoscopy must have
occurred within 3 months prior to baseline.;4. Meet the following requirements for prior or current medications for Crohn*s disease:
a. Has failed conventional therapy:
1) Is currently receiving corticosteroids and/or immunomodulators (ie, AZA, MTX, or
6-MP) at adequate therapeutic doses;
OR
2) Has a history of failure to respond to or tolerate an adequate course of corticosteroids
and/or immunomodulators (ie, AZA, MTX, or 6-MP);
OR
3) Is corticosteroid dependent or has had a history of corticosteroid dependency;
AND
b. Has not previously demonstrated inadequate response or intolerance to 1 or more TNF
antagonist therapies (ie, infliximab, adalimumab, or certolizumab pegol) as outlined in
Attachment 1 in the protocol.;5. Adhere to the following requirements for concomitant medication for the treatment of
Crohn*s disease. The following medications are permitted provided doses meeting the
requirements below are stable for or have been discontinued at least 3 weeks prior to baseline
(Week 0), unless otherwise specified.
a. Oral 5-ASA compounds.
b. Oral corticosteroids (eg, prednisone, budesonide) at a prednisone-equivalent dose of
<= 40 mg/day or <= 9 mg/day of budesonide.
c. Antibiotics being used as a primary treatment of Crohn*s disease.
d. Subjects receiving conventional immunomodulators (ie, AZA, 6-MP, or MTX) must have
been taking them for >= 12 weeks, and on a stable dose for a least 4 weeks prior to
baseline.;6. Have screening laboratory test results within the following parameters:
a. Hemoglobin >= 8.5 g/dL
b. WBCs >= 3.5 x 103/uL
c. Neutrophils >= 1.5 x 103/uL
d. Platelets >= 100 x 103/uL
e. Serum creatinine < 1.7 mg/dL
f. AST and ALT concentrations must be within 2 times the ULN range for the laboratory
conducting the test.
g. Direct (conjugated) bilirubin < 1.0 mg/dL.;7. Are considered eligible according to the following TB screening criteria:
a. Have no history of latent or active TB prior to screening. Exceptions are made for
subjects currently receiving treatment for latent TB, if there is no evidence of active TB,
or who have a history of latent TB and documentation of having completed adequate
treatment for latent TB within 3 years prior to the first administration of study agent. It is
the responsibility of the investigator to verify the adequacy of previous TB treatment and
provide appropriate documentation.
Note: The exceptions outlined above exclude subjects in countries with high multidrugresistant
TB burden (eg, South Africa, Bulgaria, and the Russian Federation), due to
potential concerns for multi-drug resistant TB.
b. Have no signs or symptoms suggestive of active TB upon medical history and/or physical
examination.
c. Have had no recent close contact with a person with active TB or, if there has been such
contact, will be referred to a physician specializing in TB to undergo additional
evaluation and, if warranted, receive appropriate treatment for latent TB prior to or
simultaneously with the first administration of study agent.
d. Within 2 months prior to the first administration of study agent, either have negative
QuantiFERON-TB Gold test (Attachment 2), or have a newly identified positive
QuantiFERON-TB Gold test in which active TB has been ruled out, and for which
appropriate treatment for latent TB has been initiated either prior to or simultaneously
with the first administration of study agent (except in countries with high multidrug resistant TB burden [eg, South Africa, Bulgaria, and the Russian Federation]), where
subjects with a newly identified positive QuantiFERON-TB Gold test result are
excluded). Indeterminate results should be handled as outlined in Section 9.1.2. A
negative tuberculin skin test (see Attachment 3) is additionally required if the
QuantiFERON-TB gold test is not approved/registered in that country. The
QuantiFERON-TB Gold In-Tube test is not required at screening for subjects with a
history of latent TB and appropriate treatment as described in 7a.
e. Have a chest radiograph (at least a posterior-anterior view), taken within 3 months prior
to the first administration of study agent and read by a qualified radiologist, with no
evidence of current active TB or old inactive TB.;8. If a woman, before entry she must be:
a. Postmenopausal, defined as
1) > 45 years of age with amenorrhea for at least 18 months,
OR
2) > 45 years of age with amenorrhea for at least 6 months and a serum follicle
stimulating hormone (FSH) level > 40 IU/mL
OR
b. Menstrual
1) Surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation,
or otherwise be incapable of pregnancy), or
2) If heterosexually active, practicing a highly effective method of birth control,
including hormonal prescription oral contraceptives, contraceptive injections,
contraceptive patch, intrauterine device, double-barrier method (eg, condoms,
diaphragm, or cervical cap, with spermicidal foam, cream, or gel), or male partner
sterilization, consistent with local regulations regarding use of birth control methods
for subjects participating in clinical trials, for the duration of their participation in the
study and for 20 weeks after receiving study agent, or
3) Not heterosexually active.
Note: Women who are not heterosexually active at screening must agree to utilize a
highly effective method of birth control if they become heterosexually active during
their participation in the study.;9. If a woman of childbearing potential, she must have a negative serum Beta-human chorionic
gonadotropin (Beta-hCG) pregnancy test at screening; and a negative urine pregnancy test at
Week 0.;10. If a man and heterosexually active with a woman of childbearing potential, he must agree to
use a double barrier method of birth control and to not donate sperm during the study and for
20 weeks after receiving study agent;11. Be willing and able to adhere to the prohibitions and restrictions specified in this protocol.;12. Sign an informed consent document indicating that they understand the purpose of and
procedures required for the study and are willing to participate in the study, and intend to
participate in the maintenance study if eligible.

Any potential subject who meets any of the following criteria will be excluded from participating
in the study. The subject will be excluded if he or she:
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 ustekinumab.;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 prior to baseline, or
8 weeks prior to baseline for intra-abdominal abscesses, provided that there is no anticipated
need for any further surgery. Subjects with active fistulas may be included if there is no
anticipation of a need for surgery and there are currently no abscesses identified.;3. Has had any kind of bowel resection within 6 months or any other intra-abdominal surgery
within 3 months prior to baseline.;4. Has a draining (ie, functioning) stoma or ostomy.;5. Has received any of the following prescribed medications or therapies within the specified
period:
a. IV corticosteroids < 3 weeks prior to baseline.
b. Other oral immunomodulatory agents (eg, 6-thioguanine [6-TG], cyclosporine,
tacrolimus, sirolimus, or mycophenolate mofetil) < 6 weeks prior to baseline.
c. Non-biologic experimental or investigational agents < 4 weeks or within 5 half-lives of
agent prior to baseline, whichever is longer.
d. Non-autologous stem cell therapy (eg, Prochymal), natalizumab, efalizumab, or biologic
agents that deplete B or T cells (eg, rituximab, alemtuzumab, or visilizumab)
< 12 months prior to baseline.
e. Anti-TNF biologic agents (eg, monoclonal antibody therapies) or other agents intended to
suppress or eliminate TNF < 8 weeks prior to baseline.
f. Other immunomodulatory biologic agents < 12 weeks or within 5 half-lives of agent prior
to baseline, whichever is longer.
g. Treatment with apheresis (eg, Adacolumn apheresis) or total parenteral nutrition (TPN)
as a treatment for Crohn*s disease < 3 weeks prior to baseline.;6. Have a stool culture or other examination positive for an enteric pathogen, including
Clostridium difficile toxin, in the last 4 months unless a repeat examination is negative and
there are no signs of ongoing infection with that pathogen.;7. Has previously received a biologic agent targeting IL-12 or IL-23, including but not limited
to ustekinumab (CNTO 1275) or briakinumab (ABT-874).;8. Has received a Bacille Calmette-Guérin (BCG) vaccination within 12 months or any other
live bacterial or live viral vaccination within 12 weeks of baseline.;9. Has a history of, or ongoing, chronic or recurrent infectious disease, including but not limited
to, chronic renal infection, chronic chest infection, recurrent urinary tract infection (eg,
recurrent pyelonephritis or chronic nonremitting cystitis), or open, draining, or infected skin
wounds or ulcers.;10. Has current signs or symptoms of infection. Established nonserious infections (eg, acute
upper respiratory tract infection, simple urinary tract infection) need not be considered
exclusionary at the discretion of the investigator.;11. Has a history of serious infection (eg, sepsis, pneumonia, or pyelonephritis), including any
infection requiring hospitalization or IV antibiotics, for 8 weeks prior to baseline.;12. Has evidence of a herpes zoster infection * 8 weeks prior to baseline.;13. Has a history of latent or active granulomatous infection, including histoplasmosis or
coccidioidomycosis, prior to screening. Refer to inclusion criteria for information regarding
eligibility with a history of latent TB.;14. Has evidence of current active infection, including TB, or a nodule suspicious for lung
malignancy on screening or any other available chest radiograph, unless definitively resolved
surgically or by additional imaging and with source document confirmation.;15. Has or ever has had a nontuberculous mycobacterial infection or serious opportunistic
infection (eg, cytomegalovirus colitis, Pneumocystis carinii, aspergillosis).;16. Is known to be infected with HIV, hepatitis B, or hepatitis C.;17. Has severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine, pulmonary,
cardiac, neurologic, cerebral, or psychiatric disease, or signs and symptoms thereof.;18. Has a transplanted organ (with exception of a corneal transplant > 12 weeks prior to
screening).;19. Has a known history of lymphoproliferative disease, including lymphoma, or signs and
symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy
and/or splenomegaly.;20. Has any known malignancy or has a history of malignancy (with the exception of basal cell
carcinoma; squamous cell carcinoma in situ of the skin; or cervical carcinoma in situ that has
been treated with no evidence of recurrence; or squamous cell carcinoma of the skin that has
been treated with no evidence of recurrence within 5 years prior to screening).;21. Has previously undergone allergy immunotherapy for prevention of anaphylactic reactions.;22. Is unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack
of easy access to veins.;23. Is known to have had a substance abuse (drug or alcohol) problem within the previous
12 months prior to baseline.;24. Has known allergies, hypersensitivity, or intolerance to ustekinumab or its excipients (refer to
Investigator's Brochure).;25. Are currently or intending to participate in any other study using an investigational agent or
procedure during participation in this study.;26. Is a woman who is pregnant, or breast-feeding, or planning to become pregnant or is a man
who plans to father a child while enrolled in this study or within 20 weeks after the last dose
of study agent.;27. Has any condition that, in the opinion of the investigator, would make participation not be in
the best interest (eg, compromise the well-being) of the subject or that could prevent, limit, or
confound the protocol-specified assessments.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening. If a subject's status changes after screening but before first dose of study agent is given, such that they now meet an exclusion criterion, they should be excluded from participation in the study.