A Multicenter, Parallel-group Study of Long-term Safety and Efficacy of CNTO 136 (sirukumab) for Rheumatoid Arthritis in Subjects Completing Treatment in Studies CNTO136ARA3002 (SIRROUND-D) and CNTO136ARA3003 (SIRROUND-T)

This is a parallel-group long-term extension (LTE) trial of studies
CNTO136ARA3002 and CNTO136ARA3003 to assess the long-term safety and efficacy
of sirukumab in subjects with moderately to severely active RA. Subjects who
have completed participation in studies CNTO136ARA3002 or CNTO136ARA3003 will
be eligible to enroll in this study. Subjects are to continue to receive the
identical sirukumab SC dose regimen of 100 mg every 2 (q2) weeks or 50 mg every
4 (q4) weeks that they were receiving upon completion of participation in
studies CNTO136ARA3002 and CNTO136ARA3003.

Primary Objective is to evaluate the long-term safety of sirukumab in subjects
with RA who are refractory to DMARDs or anti-TNF* agents.

The secondary objectives are to observe the following long-term effects of
sirukumab in subjects with RA who are refractory to DMARDs or anti-TNF* agents
on:
* Efficacy
* Pharmacokinetics
* Immunogenicity
* Pharmacodynamics
* Pharmacogenetics
* PFS-AI Usability (as defined in separate substudy protocol)

Subjects will become eligible to participate in this LTE study when they have
completed participation in studies CNTO136ARA3002 (104 weeks) or CNTO136ARA3003
(52 weeks). The purpose of this LTE study is to evaluate the safety, efficacy,
and pharmacologic effects of sirukumab for a minimum duration of 1 additional
year and a maximum total duration of approximately 5 years across the combined
protocols (CNTO136ARA3002 (2 years) or CNTO136ARA3003 (1 year) + CNTO136ARA3004
(1 to 4 years) = maximum of 5 years treatment).

The SmartJect* Autoinjector (PFS-AI) is expected to be used by the majority of
subjects in study CNTO136ARA3004. In the event PFS-AIs are unavailable at the
time of a subject*s enrollment in this protocol, sirukumab PFS-Ultrasafe
(PFS-U), the same device used in the CNTO136ARA3002 and CNTO136ARA3003 studies,
will be provided until such time as the PFS-AIs become available. Upon
availability of PFS-AI trial supplies, subjects who are newly entering the
CNTO136ARA3004 protocol will be trained on the operation of PFS-AI and perform
self-administration of study agent using PFS-AI at the Week 2 study visit and
return to the study site at Week 4 for self-administration with PFS-AI. In the
event PFS-AIs are unavailable at the time of a subject*s enrollment in this
protocol, training on the use of a PFS-AI will be provided at the next study
visit when the PFS-AI is available.

During the Week 104 visit in CNTO136ARA3002 or the Week 52 visit in
CNTO136ARA3003, subjects will sign the informed consent form (ICF) to enter
study CNTO136ARA3004. As a result, the Week 104 visit in study CNTO136ARA3002
and the Week 52 visit in study CNTO136ARA3003 will correspond to the Week 0
visit in the CNTO136ARA3004 study.

After a minimum of 1 year treatment in CNTO136ARA3004 for subjects from study
CNTO136ARA3002, or a minimum of 2 years of treatment in CNTO136ARA3004 for
subjects from CNTO136ARA3003, and after sirukumab is approved for the treatment
of RA in the subject*s country of residence, the Sponsor may no longer offer
study treatment in CNTO136ARA3004 for those specific subjects. At that point
the subject will have the opportunity to discuss treatment options with their
treating physician.

The maximum duration of participation in this study is 208 weeks, followed by
approximately 16 weeks of safety and efficacy follow-up after the
administration of the final study agent injection of sirukumab. The study will
end with the last visit for the last subject participating in the study.

Study treatment will remain blinded in CNTO136ARA3004 until the following 3
conditions have been met: the Week 52 DBL occurs in study CNTO136ARA3002, the
Week 24 DBL occurs in study CNTO136ARA3003, and the last AI usability substudy
subject completes the Week 16 visit or terminates from the study. Thereafter
treatment in study CNTO136ARA3004 becomes open-label, and placebo injections
are discontinued in the SC sirukumab 50 mg treatment group.

Subject safety will be monitored and assessments will be done through the end
of the study.
Only 1 DBL (at the end of the study) is planned. Additional data releases or
locks may occur as needed.
An Independent Data Monitoring Committee (DMC) and Clinical Events Committee
(CEC) will be commissioned for this study.

The studymedication (or placebo) is administred once per 2 weeks (1 ml)
subcutaneously. Administration switches to once per 4 weeks (1 ml
studymedication) when study becomes open-label. Total period is maximal 208
weeks.

The risks, side effects and discomforts that have been reported from our
clinical studies with sirukumab. Also mentioned are side effects that have been
reported with similar drugs, but not at this time with sirukumab.

Infections
Sirukumab is a drug that may change how the body fights infections. People
given sirukumab as well as similar medicines have reported infections. Serious,
possibly life-threatening infections that may require hospitalization have been
reported.
Sirukumab may keep a subject from developing a fever when he/she has an
infection and therefore, may hide a sign that he/she has one. The subject may
have more infections while taking this medication. Signs of an infection may
include:

* fever
* headache
* cough
* congestion
* chills
* change in urine frequency or burning feeling while passing urine
* redness or swelling of the skin or a joint
* night sweats

Blood
Sirukumab may lower the number of blood cells that help the body fight
infection and stop bleeding. Sirukumab may increase certain types of
cholesterol and may affect the liver.
The study doctor will monitors with blood tests for any abnormal results
related to the following:
* blood cells (help the body fight infection and stop bleeding)
* liver tests
* different type of cholesterol and triglycerides

Injection Site Reactions * specific for subcutaneous injections
Sirukumab will be given as an injection under the skin. After the injection,
temporary and common reactions seen at the injection site could include:
* redness
* pain
* itching
* swelling

Allergic Reactions
Allergic reactions can happen from the study medication. Some may be severe.
The following can be signs of an allergic reaction:

* chills
* rash or hives
* nausea
* flushing
* light-headedness
* irregular heartbeats
* chest tightness or wheezing
* difficulty breathing or swallowing
* low blood pressure
* swelling in face, lips, tongue and/or throat

Serious allergic reactions called anaphylaxis have been reported with
sirukumab. These can be life threatening.

Vaccines
It is unknown at this time what effect sirukumab may have on vaccines. During
this study or for 4 months after the last dose of study drug *live* vaccines
such as FluMist®, Varicella, BCG may not be administred. Other kinds of
vaccines, like tetanus and flu shots are allowed.

Antibodies to Sirukumab
Sometimes the body can make special antibodies that may increase the risk of an
allergic reaction to either sirukumab or other antibody medicines. If the
subject has an allergic reaction, he/she may not be able to have these types of
medications in the future.

Additional Known Risks from a similar drug
In people taking a similar drug the following have been reported:
gastrointestinal perforations (tears in the stomach or intestines) and a
certain type of nervous system disorder which may include symptoms such as
changes in vision, weakness, numbness or tingling. Medications like this lower
the activity of the immune system, so there may be an increased risk of some
types of cancers if the immune system cannot stop them.

Other Risks
There may be other discomforts or risks to subject from this study that are not
yet known.

Risk of Procedures
The subject may experience discomfort when a needle is inserted into the vein
to collect blood. There may be a

* slight bruise
* discoloration
* swelling
* scarring at the puncture site
* fainting

Over the course of the entire study 325 ml blood will be collected from the
subject.

Risks from use of the SmartJect Autoinjector (PFS-AI) device
In case of malfunction or improper use, the potential harms from the use of an
autoinjector are as follows: unknown quantity or quality of drug delivered,
drug contacts skin, drug swallowed, drug contacts eye, drug delivered too
shallow, drug delivered too deep, needle hits bone, needle stick injury, pain,
skin irritation, cuts, needle breaks, bruising, and air bubble under the skin.