| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 |
|
| 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 |
|
| E.2.2 | Secondary objectives of the trial |
- 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 |
|
| 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 |
|
| 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 06. Having signed a written informed consent prior to any procedure related to the study. |
|
| 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Part A:
Percentage of patients who achieved ACR20 at week 12 |
|
| 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 | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| 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 | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| 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 |
|
| 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
|
| End of trial is defined as last visit of the last subject undergoing the trial |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 39 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 39 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
