E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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
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E.2.2 | Secondary objectives of the trial |
Part B: 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 SAR153191 on top of MTX, in patients with active rheumatoid arthritis who are inadequate responders to MTX therapy |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
To collect DNA, RNA and other biomarkers for future use for the purpose of discovery of predictive biomarkers. Version 1 19 October 2009 |
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E.3 | Principal 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 05. Part B only: - At least one locally documented bone erosions (on X-ray) prior to first study drug dosing - Or, anti CCP antibody positive according to screening laboratory tests - Or, positive rheumatoid factor according to screening laboratory tests. I 06. Having signed a written informed consent prior to any procedure related to the study. |
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E.4 | Principal 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 investigator judgment. E 23. Non-healed infected skin ulcers. E 24. Received administration of any live (attenuated) vaccine within 3 months prior to the inclusion Visit (e.g. varicella-zoster vaccine, oral polio, rabies). E 25. Received vaccination by BCG within 12 months prior to screening. E 26. Known history of Human Immunodeficiency Virus (HIV) antibody; and/or positive Hepatitis B surface antigen (HBsAg), and/or positive Hepatitis C antibody (HCV) at the Screening Visit. E 27. History of recurrent herpes zoster or active herpes zoster infection. E 28. History of prior articular or prosthetic joint infection E 29. History of a hypersensitivity reaction, other than localized injection site reaction (ISR), to any biological molecule E 30. History of a hypersensitivity reaction to doxycycline, tetracycline or related compounds. E 31. Uncontrolled diabetes, defined as HbA1c ≥9.0% at the Screening Visit E 32. History of demyelinating disease E 33. Patients on dialysis E 34. Presence of any of the following laboratory abnormalities (for the central laboratory conducting the test) at the Screening Visit: - Hemoglobin <8.5g/dL - WBC <3000/μL - platelet count <100,000/μL - neutrophils <2000/μL - AST or ALT >1.5 ULN - Bilirubin >1.5 ULN unless patient diagnosed with Gilbert disease - Creatinin clearance <30ml/mn E 35. For men who are unwilling to utilize two forms of contraception a condom and a spermicidal agent. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part A: Percentage of patients who achieved ACR20 at week 12 Part B: Percentage of patients who achieved ACR20 at week 24
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 39 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 39 |