Part A:To demonstrate that SAR153191 on top of MTX is effective on reduction of signs and symptoms of rheumatoid arthritis at 12 weeksPart B:• To demonstrate that SAR153191 on top of MTX is effective on reduction of signs and symptoms of RA at 24…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective in Part A is to demonstrate that SAR153191 on top of MTX
is effective on reduction of signs and symptoms of rheumatoid arthritis at 12
weeks and to define the best dose/dosage regimen for further development.
The primary objective in Part B is to demonstrate that SAR153191 on top of MTX
is effective on reduction of signs and symptoms of rheumatoid arthritis at 24
weeks.
Secondary outcome
The main secondary objectives are:
• To demonstrate that SAR153191 on top of MTX is effective on:
- inhibition of progression of structural damage at 52 weeks
- improvement in physical function at 52 weeks
- induction of a major clinical response at 52 weeks
• To assess the safety of SAR153191 on top of MTX
• To document the PK profile of SAR153191on top of MTX, in patients with active
rheumatoid arthritis who are inadequate responders to MTX therapy.
Background summary
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory autoimmune
disease, primarily targeting the synovial membrane of diarthrodial joints. This
process can result in progressive joint destruction, chronic disability and
shortened life expectancy. Interleukin-6 (IL-6) is a key
cytokine involved in the pathogenesis of RA causing inflammation and joint
destruction (1). Inhibition of IL-6 signaling through blockade of the IL-6
receptor (IL-6R) is an effective new therapeutic modality for RA as
demonstrated by Tocilizumab, a humanized monoclonal antibody
to IL-6 receptor, approved in Europe in January 2009 for treatment of RA and
currently under review by the FDA.
SAR153191 is administered subcutaneously, which provides the advantage over
Tocilizumab, intravenous, of a self administration option which is generally
more convenient. It is expected than a human mAb will provide less immunologic
reactions compared to a humanized mAb.
Study objective
Part A:
To demonstrate that SAR153191 on top of MTX is effective on reduction of signs
and symptoms of rheumatoid arthritis at 12 weeks
Part B:
• To demonstrate that SAR153191 on top of MTX is effective on reduction of
signs and symptoms of RA at 24 weeks
Study design
This study is a worldwide, double-blind, placebo controlled, randomized study
in patients with rheumatoid arthritis with an inadequate response to MTX. It
will include 2 parts using an operationally seamless design.
The first part (Part A) of the study is a 12 week, 6-arm dose ranging part
intended to select the 2 best dose regimens based on efficacy (reduction in
signs and symptoms) and safety.
The second part (Part B) of the study is a 52 week part to confirm the efficacy
and safety of these 2 selected dose regimens on reduction in signs and
symptoms, inhibition of progression of structural damage, improvement in
physical function and induction of major clinical response.
The operationally seamless design nature of this study resides in the fact that
Part B is starting to enrol patients just after the last patient is randomized
in Part A without waiting for the dose selection based on its results. Thus
part B patients belong to two distinct cohorts according to the time of their
enrolment:
• Cohort 1 of patients randomized before the dose selection: these patients are
randomized into 6-arm (as the ones of Part A). After dose selection, the
patients randomized in the 2 selected doses and the placebo regimens continue
the 52-week trial but the ones
randomized in the 3 other arms are discontinued from the present study but
proposed to join an open label extension (see LTS11210). Not conducted in the
Netherlands.
• Cohort 2 of patients randomized after the dose selection: these patients are
randomized into 3-arm, the 2 selected ones and placebo.
In summary, this operationally seamless design is using a learning stage (Part
A) to select the relevant dose regimens and a confirmatory stage (Part B) to
test the selected dose regimens, without interruption of inclusions but
ensuring complete protection of the blindness of the trial. This proposed
design is consistent with regulatory agencies initiatives (2006 Conference on
adaptive trial design FDA, 2009 EMEA workshop) to streamline and improve drug
development processes. The design of this study has been discussed and agreed
both by the FDA and the EMEA.
Intervention
Screening phase: 4 weeks
Dubble-blind treatment phase part A: Max. 12 weeks, weekly injection with
SAR153191 or placebo
Dubble-blind treatment phase part B: Max. 52 weeks, weekly injection with
SAR153191 or placebo
Study burden and risks
Risks are related to blood sampling and possible side effect 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.
Kampenringweg 45 D-E
2803 PE Gouda
Nederland
Kampenringweg 45 D-E
2803 PE Gouda
Nederland
Listed location countries
Age
Inclusion criteria
• Diagnosis of rheumatoid arthritis >= 3 months duration
• Active disease defined as:
- at least 8/68 tender joints and 6/66 swollen joints
- hs-CRP >10mg/l
- Continuous treatment with MTX for at least 12 weeks prior to baseline and on stable dose (10mg/w-25mg/w) for 6 weeks prior to screening.
• Part B only:
- Bone erosion based on documented X-ray prior to first study drug dosing
- Or Cyclic Citrullinated Peptide CCP positive
- Or Rheumatoid Factor (RF) positive.
Exclusion criteria
• Age <18 years or >75 years,
• Treatment with DMARDs (other than MTX) within 4 weeks or 12 weeks prior to screening (depending on DMARDs).
• Past history of non response to prior TNF or biologic treatment,
• Any past or current biologic agents for the treatment of RA within 3 months,
• Use of parenteral glucocorticoids or intraarticular glucocorticoids within 4 weeks prior to screening visit
• Use of oral glucocorticoid greater than 10mg/day or equivalent/day, or a change in dosage within 4 weeks prior to baseline visit.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-016266-90-NL |
| CCMO | NL31838.058.10 |
| Other | Zie sectie J. |