A multi-center, uncontrolled extension study evaluating efficacy and safety of SAR153191 on top of DMARDs in patients with active Rheumatoid Arthritis (RA)

Rheumatoid arthritis (RA) is a chronic, debilitating disease that primarily
affects the synovial membrane of diarthrodial joints. Currently, treatment of
RA involves the use of nonsteroidal anti-inflammatory drugs (NSAIDs),
glucocorticoids and disease modifying anti-rheumatic drugs (DMARDs).
Methotrexate, sulfasalazine, hydroxychloroquine and leflunomide are DMARDs that
have been used by rheumatologists for many years.
Introduction of biologic agents, especially inhibitors of TNF-α, has greatly
improved the therapeutic options available for treating RA; however, no
therapeutic modality provides either universal or complete control of disease
and safety remains one of the key issues with anti-TNF-α treatment.
Besides early benefit/risk of biologics, the long term outcome of RA remain a
critical question: long term use of biologics have been associated with
immunosuppression and effects on the development of infections, malignancies,
demyelinating events, lupus like events, etc*To deal
with this concern, long-term data are needed to allow comparison with well
established adverse events in this population.

The primary objective of the study is to evaluate the long term safety of
SAR153191 in patients with RA on top of DMARDs.
The secondary objective of the study is finding the percentages of patients who
reach ACR20, DAS28 and EULAR response overtime.

This is a multicenter, multinational open label long term study, only for
patients with RA who participated in the study EFC11072 and completed Part A
(12 weeks of treatment) or Part B (52 weeks of treatment) or patients who were
randomized in Part B of the study EFC11072 in a
treatment arm subsequently not retained following pivotal dose selection.
Patients need to sign a specific informed consent in order to participate in
the LTS11210 study.
Initially patients will receive 150 mg of SAR153191 SC weekly for up to 260
weeks of treatment (from the first intake of SAR153191 in the study EFC11072)
or until commercially available, whichever comes first. During screening at V1
(D-7 to D-1) patients will have a safety evaluation
and will be assessed for concomitant medications and eligibility to the study.
The last treatment visit in the study EFC11072 will be used as the screening
visit. In addition patients will have a CPK test (only at screening).
At Day 1 (week 0) after confirmation of eligibility, they will receive the
administration of the first dose of SAR153191 150 mg SC at the investigational
site and will be reminded on how to self inject.
They will be reminded to self inject 7 days apart. At dosing time points
occurring outside site visits, SAR153191 can be injected by the patient
himself, or by a trained caregiver.
Patients will return for follow up visits according to the flow chart for
additional laboratory testing, questionnaires and joint examination.
Initially, patients will receive the highest dose tested in EFC11072 part A,
currently 150 mg weekly. This dose will be switched to a lower dose regimen in
case of discontinuation of this treatment arm, or selection of a lower pivotal
dose regimen.
The Investigators will check all laboratory parameters during this study. In
case of increased LFTs, or decreased neutrophil counts, a reduction of dose,
initially 150 mg every other week will be permitted, as well as adjustment of
DMARDs dosage.
Patients who discontinue treatment before the planned end of treatment should
have a safety follow up visit, Visit 29, six weeks after the end of treatment.

Open label long term study treatment: Max. 260 weeks, weekly injection with
SAR153191.

Risks are related to blood sampling, X-ray and possible side effects of the
(administration of) the study drug. The burden for the patient will be the
number of visits to the center as part of the trial. In addition, the patient
is asked to fill in a diary.