A Phase 3 Randomized, Open-Label Study to Assess the Efficacy, Safety,and Pharmacokinetics of Golimumab Treatment, a Human anti-TNFα Monoclonal Antibody, Administered Subcutaneously in Pediatric Participants with Moderately to Severely Active Ulcerative Colitis

Golimumab was studied in a Phase 3 program of adults with moderately to
severely active UC.
This program demonstrated that golimumab is an effective anti-TNFα therapy in
adults and was
generally well-tolerated, with a safety profile consistent with that observed
for golimumab in
other indications. Studies C0524T17 and C0524T18 were the basis for the
approval of
golimumab in adults with moderately to severely active UC in both the US (15
May 2013) and
the EU (19 September 2013).
Golimumab has the potential to offer pediatric participants with moderately to
severely active
UC a safe and effective therapy with a convenient SC injection option given
every 4 weeks
(q4w).

Primary Objectives
* To evaluate the efficacy of golimumab in inducing clinical remission as
assessed by the Mayo score,
in pediatric participants with moderately to severely active ulcerative colitis
(UC).
* To evaluate the safety profile of golimumab, in pediatric participants with
moderately to severely
active UC.
Secondary Objectives
* To evaluate the efficacy of golimumab in inducing clinical response as
assessed by the Mayo Score
and clinical remission as measured by the Pediatric Ulcerative Colitis Activity
Index Score (PUCAI)
Score.
* To evaluate the efficacy of golimumab on endoscopic healing.
* To evaluate the efficacy of golimumab during the long-term phase.
* To evaluate the effect of golimumab on additional efficacy and quality of
life measures
* To evaluate the PK and exposure response of golimumab during short- and
long-term phases.
Additional Objective (Usability Assessment Substudy)
* To evaluate the potential for at home use of golimumab in the participant
population >=45kg during
the Usability Assessment Substudy.

This is a multicenter, randomized, open-label golimumab study in pediatric
participants aged 2 to 17
years with moderately to severely active UC, defined as a baseline Mayo score
of 6 through 12, inclusive,
with an endoscopy subscore of >=2.
In this study, the remission rate of golimumab in pediatric participants will
be formally compared with a
historical placebo remission rate derived from a meta-analysis of adult Phase 3
UC studies of golimumab
and other products approved in this indication utilizing similar populations
and endpoints.
This study will also include a reference infliximab arm for the purpose of
determining assay sensitivity
only if the success criteria are not met (versus historical placebo). No formal
comparisons between
golimumab and infliximab will be performed.
Endoscopies performed for this study are to be performed using study software
and submitted for central
review. Scoring for disease activity based on endoscopic appearance is to be
performed both by the local
endoscopist and the central reviewer. All decisions to initiate (Week 0) or
continue therapy (Week 6) will
be based on local reads. Analyses of the primary and major secondary endpoints
will be based on locally
read endoscopy measures. Analyses of these endpoints will also be performed
using the centrally read
endoscopy measures.
This 54-week study will consist of a 6-week short-term phase and a 48-week
long-term phase followed by
a study extension (for eligible golimumab-treated participants).
Beginning at Week 58, participants who are eligible to continue receiving
golimumab in the study
extension will be offered the option for self-administration (at least 12 years
old and body weight >=45 kg)
or caregiver-administration (any age but body weight >=45 kg). This is optional;
if a pediatric participant
or caregiver elects against self- or caregiver-administration, the health care
professional will continue to
administer injections in this study.
An internal Data Monitoring Committee (consisting of Sponsor members [a
gastroenterologist, a clinician
and a statistician at a minimum] outside of the study team), will be
established to monitor safety data (for
both golimumab and infliximab treatments arms) on an ongoing basis until all
participants reach the
Week 54 visit or terminate the study prior to the Week 54 visit.

Golimumab
During the short-term phase, pediatric participants will receive dose regimens
of subcutaneous (SC)
golimumab at Week 0 and Week 2 based on body weight as shown in Table I below.
Participants must
weigh >=10 kg and be >70 cm tall. This is the lower range of weight and height
that the pre-filled pen
(PFP-V) has been validated for to deliver SC golimumab. This limit accommodates
>97% of all 2-year
old girls based on published growth charts (www.cdc.gov/growthcharts).
Participants' golimumab doses
for all administrations through Week 10 (inclusive) will be based on the
participants' weight and height at
Week 0 or, if not available, the most recent height and weight from screening.
The same weight and
height should be used through Week 10. Golimumab doses from Week 14 through
Week 54 will be based
on the participants' weight and height obtained with that week*s visit or the
height and weight measured at
the previous site visit. In the study extension, golimumab doses will be based
on the participants' most
current weight and height or the last recorded height and weight.
At Week 6, all participants will be evaluated for clinical response;
participants in clinical response will
continue receiving open-label golimumab during the long-term phase.
Participants not in clinical response (as evaluated by the Mayo score) at Week
6 may have study agent
discontinued (and complete a safety follow-up at least 16 weeks after the last
administration of
golimumab) OR may continue receiving golimumab for up to 2 additional doses at
Weeks 6 and 10 as
specified in Table I at the discretion of the Investigator. At Week 14, these
participants who received the
2 additional doses will need to demonstrate a partial Mayo response to continue
on in the study;
participants in partial Mayo response will continue receiving open-label
golimumab (q4w) during the
long-term phase (Table I). Participants who received the 2 additional doses and
are not partial Mayo
responders at Week 14 will have study intervention discontinued and should
complete a final safety
follow-up at least 16 weeks following the last administration of study
intervention.

Infliximab
All participants in the infliximab treatment arm will be administered
infliximab 5 mg/kg at Weeks 0 and
2. Starting at Week 6, infliximab administrations of 5 mg/kg will continue q8w
through Week 46 for
those participants in clinical response at Week 6. Infliximab doses for all
administrations through Week 8
(inclusive) will be based on the participants' weight at Week 0 or, if not
available, the most recent weight
from screening. The same weight should be used through Week 8. Infliximab doses
from Week 14
through Week 46 will be based on the participants' weight obtained with that
week*s visit or the weight
measured at the previous site visit.
For those participants not in clinical response at Week 6 (as defined by the
Mayo score), or participants
who were in response at Week 6 but have a clinical flare in their UC (defined
in Section 6.5.3) an
additional step-wise dose escalation approach may be taken at the investigators
discretion. The first step is
a dose increase at Week 6 to 10 mg/kg [capped at 1 gm] q8w or 5 mg/kg at Weeks
6 and 8, and 10 mg/kg
(capped at 1 gm) at Week 14 and q8w thereafter, respectively). At Week 14, if
the participant has
demonstrated a partial Mayo response, they will continue to receive infliximab
10mg/kg q8w.
Additionally, if the participant has not achieved a partial Mayo response by
Week 14, starting at the
Week 14 visit, the investigators can also shorten the interval between doses to
q4w.
At Week 22, those participants who had received an escalation in their
infliximab dosing to 10 mg/kg
q4w will need to demonstrate a partial Mayo response to continue in the study.
Participants in partial
Mayo response will continue receiving open-label infliximab 10 mg/kg q4w
through Week 46.
Participants who have not achieved a partial Mayo response at Week 22 will have
study intervention
discontinued and should complete a final safety follow-up at least 8 weeks
following the last
administration of infliximab.
Participants who dose-escalate in response to a UC flare after Week 6 will be
reassessed after two
administrations at the new higher dose. Participants in partial Mayo response
will continue receiving
open-label infliximab through Week 46 at the new higher dose. Participants who
have not achieved a
partial Mayo response will have study intervention discontinued and should
complete a final safety visit
at least 8 weeks following the last administration of infliximab.
Finally, while dose escalation should be based on clinical criteria as
described above, investigators at their
discretion may utilize infliximab serum levels to assist their decision making.
This approach was chosen
as it most closely mimics clinical practice in treatment of pediatric UC,
allowing investigators some
flexibility in dosing to treat their patients. After the Week 54 evaluations,
participants receiving
infliximab will be transitioned off the study to standard medical care.

The expected therapeutic effect justifies the burden and risks for the
participants.