RESTART C0168Z05 Rheumatoid Arthritis Study

Study Overview
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Brief Summary
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The purpose of this study is to assess the effectiveness of treatment in patients with active rheumatoid arthritis who are having an inadequate response to at least 3 months of treatment with etanercept or adalimumab in addition to methotrexate.

Detailed Description
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This is a Phase 4, multi center, open-label, assessor blinded, switch study of infliximab in patients with active rheumatoid arthritis who are receiving methotrexate and are having an inadequate response to their current treatment with etanercept or adalimumab. The last dose of etanercept must have been at least 1 week but not more than 2 weeks prior to the first infliximab study infusion. The last dose of adalimumab must have been administered at least 2 weeks but not more than 4 weeks prior to the first infliximab study infusion. The study will be conducted for 30 weeks and will include 200 patients. All eligible patients will receive 3 mg/kg infliximab infusions (drug given into a vein) at weeks 0, 2, and 6 and every 8 weeks thereafter, if they achieve a European League Against Rheumatism (EULAR) response on their current dose of infliximab. Patients who do not achieve a EULAR response will increase their dose from 3mg/kg to 5 mg/kg at week 14. Patients who do not achieve a EULAR response at week 22 will increase from either 3 mg/kg to 5 mg/kg or from 5mg/kg to 7 mg/kg. The last study infusion will take place at week 22. The last study visit for effectiveness evaluations will take place at week 26. A week 30 follow-up visit will be performed for adverse events and tuberculosis evaluations, health economics assessments, and review of concomitant medications. All patients who end the study early will be required to complete all assessments. Patients will receive 3 mg/kg infliximab infusions at weeks 0, 2, and 6. If patients achieve European League Against Rheumatism (EULAR) response, they will remain on their current dose. Patients who do not demonstrate a EULAR response will increase their infliximab dose from 3 mg/kg to 5 mg/kg at week 14. At week 22, patients will also increase their infliximab dose from 3 mg/kg to 5mg/kg or from 5 mg/kg to 7mg/kg if they do not demonstrate a EULAR response.

Official Title
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A Phase 4, Multicenter, Open-Label, Assessor-Blinded Switch Study of the Efficacy and Safety of Infliximab (REMICADE) in Patients With Active Rheumatoid Arthritis Who Are Responding Inadequately to Etanercept (ENBREL) or Adalimumab (HUMIRA).

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: Infliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have rheumatoid arthritis Patients must have greater than or equal to 6 tender joints and greater than or equal to 6 swollen joints Patients must have inadequate disease response to etanercept or adalimumab Patients must have received etanercept or adalimumab in combination with methotrexate for a minimum of at least 3 months prior to the screening visit. The last dose of etanercept must have been given at least 1 week but not more than 2 weeks prior to first infliximab infusion. The last dose of adalimumab must have been administered at least 2 weeks but not more than 4 weeks prior to first infliximab infusion. Exclusion Criteria: Patients who have a history of latent or active TB Have inflammatory disease other than rheumatoid arthritis Have had a chronic or recurrent infectious disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 001<br>Infliximab3 mg/kg at week 0,2,6; Increase to 5mg/kg or 7 mg/kg based on EULAR response | Biological: Infliximab<br>* 3 mg/kg at week 0,2,6; Increase to 5mg/kg or 7 mg/kg based on EULAR response<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Patients Who Achieved a EULAR (The European League Against Rheumatism) Response at Week 10 | Percent of patients who achieved EULAR response at Week 10. EULAR response is defined based on the DAS28 score and the EULAR response criteria (Van Gestel et al, 1996 and 1999). At a given visit, patients with a DAS28 score of ≤ 5.1 are considered EULAR responders if the improvement from baseline in their DAS28 score is greater than 0.6; Or patients with a DAS28 score > 5.1 are considered EULAR responders if the improvement from baseline in their DAS28 score is > 1.2. | Week 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Patients Who Acheived EULAR Response at Week 10 and Maintained Through Week 26 Without Infliximab Dose Increase | Percent of patients who achieved EULAR response at Week 10 and maintained through Week 26 without infliximab dose increase | Week 26 | 
| Percent of Patients Who Achieved EULAR Response at Week 26, Regardless of EULAR Response Status at Weeks 10, 14, and 22, With or Without Dose Increase Prior to Week 26 | Percent of patients who achieved EULAR response at Week 26, regardless of EULAR response status at Weeks 10, 14, and 22, with or without dose increase prior to Week 26 | Week 26 | 
| Change From Baseline in Physical Function (HAQ) | Change from baseline in physical function (HAQ) at Week 10. HAQ assesses the degree of difficulty a person has in accomplishing tasks. A lower HAQ score indicates less difficulty. Change from baseline is computed as Week 10 value minus baseline value. A negative value in change from baseline indicates an improvement. | Week 10 | 
| Change From Baseline in Physical Function (HAQ) | Change from baseline in physical function (HAQ) at Week 26. HAQ assesses the degree of difficulty a person has in accomplishing tasks. A lower HAQ score indicates less difficulty. Change from baseline is computed as Week 26 value minus baseline value. A negative value in change from baseline indicates an improvement. | Week 26 | 
| Percent of Patients Who Achieved ACR20 at Week 10 | Percent of patients who achieved ACR20 at Week 10. A patient is considered achieving ACR20 if the following two conditions are met: 1) An improvement of ≥ 20% from baseline in both the swollen joint count (66 joints) and tender joint count (68 joints; 2) An improvement of ≥ 20% from baseline in at least 3 of the following 5 assessments:Patient's assessment of pain visual analog scale (VAS), Patient's global assessment of disease activity (VAS), Evaluator's global assessment of disease activity (VAS), Patient's assessment of physical function as measured by the HAQ disability index, and CRP. | Week 10 | 
| Percent of Patients Who Achieved ACR20 at Weeks 26. | Percent of patients who achieved ACR20 at Weeks 26. A patient is considered achieving ACR20 if the following two conditions are met: 1) An improvement of ≥ 20% from baseline in both the swollen joint count (66 joints) and tender joint count (68 joints; 2) An improvement of ≥ 20% from baseline in at least 3 of the following 5 assessments:Patient's assessment of pain visual analog scale (VAS), Patient's global assessment of disease activity (VAS), Evaluator's global assessment of disease activity (VAS), Patient's assessment of physical function as measured by the HAQ disability index, and CRP. | Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rheumatoid arthritis, remicade, infliximab, Centocor, etanercept, enbrel, adalimumab, humira, restart, swollen joints, tender joints.