A randomized, double-blind, placebo-controlled, multicenter, two-part, dose ranging and confirmatory study with an operationally seamless design, evaluating efficacy and safety of SAR153191 on top of methotrexate (MTX) in patients with active rheumatoid arthritis who are inadequate responders to MTX therapy - MOBILITY

• Register: EUCTR
• Last refreshed on: 26 November 2013
• Main ID: EUCTR2009-016266-90-LT
• Date of registration: 25/01/2010
• Prospective Registration: Yes
• Primary sponsor: Sanofi-aventis Recherche & Développement
• Public title: A randomized, double-blind, placebo-controlled, multicenter, two-part, dose ranging and confirmatory study with an operationally seamless design, evaluating efficacy and safety of SAR153191 on top of methotrexate (MTX) in patients with active rheumatoid arthritis who are inadequate responders to MTX therapy - MOBILITY
• Scientific title: A randomized, double-blind, placebo-controlled, multicenter, two-part, dose ranging and confirmatory study with an operationally seamless design, evaluating efficacy and safety of SAR153191 on top of methotrexate (MTX) in patients with active rheumatoid arthritis who are inadequate responders to MTX therapy - MOBILITY
• Date of first enrolment: 06/09/2010
• Target sample size: 1740
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016266-90
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Czech Republic, Estonia, Finland, Germany, Greece, Hungary, Lithuania, Netherlands, Portugal, Romania, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
I 01. Diagnosis of Rheumatoid Arthritis (RA) as defined by the 1987 revised American College of Rheumatology (ACR) criteria with disease duration of no less than 3 months and ACR class I-III.
I 02. Patients must be on a stable dose of MTX (10 to 25 mg/week) for a minimum of 6 weeks prior to the Screening Visit and intend to continue for the duration of the study.
I 03. Patients must have been treated with, and tolerated, a minimum of 12 weeks treatment with methotrexate (MTX) prior to the inclusion visit.
I 04. Patient with moderate to severe active disease defined as:
- At least 8 out of 68 joints assessed as painful or tender on motion at both screening and baseline visits, and,
- At least 6 out of 66 joints assessed as swollen at both screening and baseline visits,and,
- hs C-Reactive Protein >10mg/L at screening visit
I 06. Having signed a written informed consent prior to any procedure related to the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
E 01. Male or female <18 years of age or >75 years
E 02. Weight <50kg for men or <45kg for women or >110 kg
E 03. Autoimmune disease other than RA or significant systemic involvement
E 04. History of or current acute inflammatory joint disease other than RA, or RA diagnosed before the age of 16.
E 05. Treatment with oral prednisone or equivalent >10mg per day within 4 weeks prior to the Inclusion Visit or Use of parenteral or intra-articular glucocortisteroids within 4 weeks prior to the Screening Visit
E 06. Start treatment or change dose of current treatment with NSAIDs/COX2 inhibitors or oral corticosteroids for 4 weeks prior to baseline.
E 07. Current treatment with DMARDS/immunosuppressive agents other than MTX.
E 08. Past history of non response to prior therapy with TNF antagonist or a biologic treatment.
E 09. Prior therapy with a TNF antagonist or any other biologic agents within 3 months prior to inclusion.
E 10. Participation in any clinical research study evaluating another investigational drug or therapy within 60 days or at least 5 half-lives, whichever is longer, of the investigational drug, prior to the Screening Visit
E 11. History of malignancy other than carcinoma in-situ of the cervix, or adequately treated, non-metastatic squamous or basal cell carcinoma of the skin within five years prior to Screening Visit. History of lymphoproliferative disease or possible current lymphoproliferative disease.
E 12. History of alcohol or drug abuse within the 5 years prior to the Screening Visit.
E 13. Have a history or presence of significant other concomitant illness according to the Investigator judgment.
E 14. Conditions/situations such as:
- Patients with short life expectancy
- Patients with conditions/concomitant diseases making them non-evaluable for the
primary efficacy endpoint
- Requirement for concomitant treatment that could bias primary evaluation
- Impossibility to meet specific protocol requirements (e.g. need for hospitalization, etc)
- Patient is the Investigator or any sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol
- Uncooperative or any condition that could make the patient potentially non-compliant with the study procedures
E 15. Patients not willing to take folic acid with the MTX dose, to minimize toxicity
E 16. Pregnant or breast-feeding women,
E 17. Previous exposure to SAR153191
E 18. For women of childbearing potential, unwillingness to utilize adequate contraception or not become pregnant during the full course of the study.
E 19. Any subject who has had surgery within 4 weeks prior to the Screening Visit or with planned elective surgery.
E 20. Patients with a latent or active tuberculosis (TB) defined as:
- Any signs or symptoms suggestive of active TB upon medical history or clinical
examination.
- Subjects with a positive QuantiFERON, TB gold test or tuberculin test (PPD skin test
=10mm) at screening. (see Section 10.2).
- Chest radiograph within 3 months prior to the inclusion visit.
- Subjects with close contact with a person with active tuberculosis.
E 21. Patients with a history of resolved Listeria or tuberculosis (unless documented adequately treated).
E 22. Fever (=38°C) or persistent chronic or active recurring infection requiring treatment with antibiotics, antivirals, or antifungals within 4 weeks prior to the Screening Visit, or history of frequent recurrent infections unacceptable per

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 12.0 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Product Name: not applicable
Product Code: SAR153191
Pharmaceutical Form: Solution for injection
Current Sponsor code: SAR153191
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: not applicable
Product Code: SAR153191
Pharmaceutical Form: Solution for injection
Current Sponsor code: SAR153191
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: not applicable
Product Code: SAR153191
Pharmaceutical Form: Solution for injection
Current Sponsor code: SAR153191
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Part A:
Percentage of patients who achieved ACR20 at week 12

Secondary Objective: - To assess the safety of SAR153191 on top of MTX
- To document the PK profile of SAR153191 on top of MTX, in patients with active rheumatoid arthritis who are inadequate responders to MTX therapy

Main 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

Secondary ID(s)

EFC11072

2009-016266-90-ES