A Study to Evaluate Efficacy and Safety of Ustekinumab Re-induction Therapy in Participants With Moderately to Severely Active Crohn's Disease

This study compares the efficacy and safety of a single weight-tiered based IV re-induction
dose of approximately 6 mg/kg ustekinumab versus continuing with regular SC q8w 90 mg
ustekinumab administration. It consists of screening (5 weeks); treatment period (Week 0 to
24); and safety follow up visit (20 weeks after last dose). The primary hypothesis is that a
single IV re-induction dose of ustekinumab is superior to continuing with regular SC q8w
maintenance treatment as measured by clinical response after 16 weeks of treatment. Study
assessments will include Crohn's disease activity index (CDAI), video ileocolonoscopy,
patient-reported outcomes (PROs), laboratory evaluations, biomarkers, review of concomitant
medications and adverse events (AEs), and evaluation of serum concentrations of study agent
as well as development of antibodies to study agent. All participants will be randomly
assigned to receive either ustekinumab IV re-induction or regular SC q8w 90 mg ustekinumab
injection at baseline in a double dummy design. No participants will be treated with placebo
only.

Inclusion criteria:

- A history of 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

- Initially responded to ustekinumab induction therapy, administered according to the
local label, followed by secondary loss of response (LoR) to ustekinumab. Secondary
LoR to ustekinumab is defined as active disease at study baseline, proven by a Crohn's
Disease Activity Index (CDAI) score of greater than or equal to (>=) 220 and <=450
with at least one of the following: Elevated C-reactive protein (CRP) (>3.0 milligram
per liter [mg/L]); and/or elevated Fecal calprotectin (FeCa) >250 milligram per
kilogram [mg/kg]); and/or endoscopy (performed within the 3 months before baseline)
with evidence of active Crohn's disease during the current disease flare (that is
[i.e.], ulcerations in the ileum and/or colon)

- Participants receiving either oral 5-aminosalicylic acid (5-ASA) compounds, oral
corticosteroids (for example {e.g.}, prednisone, budesonide) at a
prednisone-equivalent dose of <=40 mg/day or <=9 mg/day of budesonide, antibiotics
used as the primary treatment of Crohn's disease, or conventional immunomodulators
(i.e., azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]) are
permitted providing the doses indicated are stable before baseline or have been
discontinued before baseline within the protocol defined durations

Exclusion Criteria:

- 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

- 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
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 there
are currently no abscesses identified

- Any kind of bowel resection within 6 months or any other intra-abdominal surgery
within 3 months before baseline

- A draining (i.e., functioning) stoma or ostomy

- Received any of the following prescribed medications or therapies within a specified
period including any off-label use of ustekinumab, additional IV re-induction or
shortened frequency of subcutaneous dose administration, after the initial
weight-tiered based IV induction dose of ustekinumab