E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid Arthrithis, Nos |
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MedDRA Classification |
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 |
To demonstrate that the abatacept in combination with methotrexate will demonstrate a greater reduction in disease activity than placebo in combination with methotrexate as measured by the disease activity score (DAS28) at 6 months (Day 197). |
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E.2.2 | Secondary objectives of the trial |
* To demonstrate that infliximab in combination with methotrexate will demonstrate a greater reduction in disease activity than placebo in combination with methotrexate as measured by the disease activity score (DAS28) at 6 months. * Compare the reduction in disease activity over time as measured by the DAS28 area under the curve (DAS28AUC) over 12 months in subjects receiving abatacept versus infliximab in combination with methotrexate. * Assess the change in physical function and the subject’s health-related quality of life as measured by the disability index of the HAQ and the SF-36 questionnaire respectively, in subjects receiving placebo, abatacept, or infliximab in combination with methotrexate at 6 months and 12 months * Determine the proportion of subjects treated with abatacept or infliximab at 12 months who demonstrate a good, moderate or no response according to the EULAR response criteria. (see protocol for additional secondary objectives). |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
* Subject is willing to participate in the study and signed the informed consent. * Subjects must meet the criteria of the American Rheumatism Association (1987) for the diagnosis of rheumatoid arthritis and the American College of Rheumatology (1991) functional Classes I, II, or III. (Refer to protocol appendices 1 and 2.) * Subjects must have been taking methotrexate for at least 3 months at a weekly dose of at least 15 mg, and at a stable dose for 28 days prior to treatment (Day 1) * Men and women, ages 18 ≤ 75 years old. Men and Women of childbearing potential are eligible if they are practicing effective contraceptive measures. * Methotrexate alone: Subjects who are treated only with methotrexate will not require washout. * Methotrexate plus other DMARDs: Subjects who are treated with methotrexate in combination with another anti-rheumatic treatment (DMARD) will require washout of the other DMARD. * Drug stabilization requirements (except methotrexate) a) All DMARDs (except methotrexate) should be discontinued at least 28 days prior to treatment (Day 1). i) In the case of leflunomide, the subject can be washed out with cholestyramine according to manufacturer recommendations. b) Oral corticosteroid treatment must have been reduced to the equivalent of 10 mg prednisone daily for 28 days and stabilized for at least 25 out of 28 days prior to treatment (Day 1). For Subjects Receiving Methotrexate Alone: At randomization (Day 1), subjects must have the following disease activity: a) 10 or more swollen joints (66 joint count) and b) 12 or more tender joints (68 joint count) and c) C-reactive protein (CRP) ≥ 1 mg/dL (Result used from screening visit) For Subjects Receiving Other DMARDs Plus Methotrexate: At screening visit, subjects must have the following disease activity: a) 6 or more swollen joints (66 joint count) and b) 8 or more tender joints (68 joint count) and c) No restriction on CRP IN ADDITION All subjects who are receiving other DMARDs plus methotrexate therapy at the screening visit must undergo a 28 day washout period of their other anti-rheumatic treatment (DMARD) (other than methotrexate). After washout at randomization (Day 1), subjects must have the following disease activity:
a) 10 or more swollen joints (66 joint count) and b) 12 or more tender joints (68 joint count) and c) C reactive protein (CRP) ≥ 1 mg/dL. (Result used from Day -3 visit). |
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E.4 | Principal exclusion criteria |
* WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 10 weeks after the last infusion of abatacept * Any previous or current medical conditions that are contraindications to the use of TNF blocking agents. (Please refer to Appendix 11 and 12 Remicade Labels) * Subjects who have previously received treatment with an approved biologic RA therapy (Infliximab, Etanercept, Anakinra, Adalimumab). * Subjects who have failed more than 3 oral DMARDs. * Subjects with active vasculitis of a major organ system (except for subcutaneous rheumatoid nodules). * Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease. * Female subjects, who have not had age and/or risk factor appropriate breast cancer screening or who have had a breast cancer screening study that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations * Subjects with a history of cancer within the last five years (other than non-melanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to dosing. * Subjects with active tuberculosis (TB) requiring treatment within the previous 3 years. Subjects with a positive PPD at screening will not be eligible for the study unless active TB infection has been ruled out, they have initiated treatment for latent TB for at least 4 weeks prior to dosing of study drug, and they have a negative chest x-ray at enrollment. * Hepatitis B surface antigen-positive subjects. * Hepatitis C antibody-positive subjects who are also RIBA-positive or PCR-positive. * Subjects with any of the following laboratory values: • Hgb < 8.5 g/dL. • WBC < 3,000/mm3 (3 x 109/L) • Platelets < 100,000/mm3 (100 x 109/L). • Serum creatinine > 2 times upper limit of normal. • Serum ALT or AST > 2 times upper limit of normal.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point will be the comparison of abatacept versus placebo for changes from baseline to 6 months (Day 197) in the DAS28. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
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) | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Placebo arm for 6 months. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |