An Efficacy and Safety Study of Infliximab in Participants With Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness of iInfliximab plus methotrexate (MTX) in treatment of Rheumatoid rheumatoid Arthritis arthritis (RA) (it is an autoimmune disease that causes pain, swelling, stiffness and loss of function in joints) in participants with moderate disease versus participants with severe disease and to compare the efficacy and safety of the MTX subgroups.

Detailed Description
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This is an open-label (all people know the identity of the intervention), multi-center (study conducted in more than 1 center), prospective (study following participants forward in time) study comparing the American College of Rheumatology (ACR) scores of participants with moderate RA (defined as having a score greater than 3.2, but less than 5.1 on the Disease Activity Score 28 [DAS 28]) to those participants with severe RA (defined as having a score greater than 5.1 on the DAS 28 score) disease while being treated with infliximab and MTX. DAS evaluates RA activity by several parameters including the number of swollen and tender joints and the participant's own assessment of their pain. Participants will receive infliximab 3 milligram (mg) per kilogram (kg) intravenous infusion (drug given into a vein) (over no less than 2 hours) at Weeks 0, 2, 6, 14 and 22 along oral MTX in a stable dose of 7.5 to 20 mg per week (equal to the dose used before participation in the study) for 22 Weeks. Participants will have a follow-up visit on Week 26. Efficacy will primarily be assessed by the percentage of participants obtaining ACR20, ACR50 and ACR70 response at Week 26. Participants' safety will be assessed throughout the study.

Official Title
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A Multi-Center, Pre-Marketing Clinical Trial to Evaluate the Efficacy and Safety of Infliximab Treatment on Rheumatoid Arthritis

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: Infliximab
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who have a definitive diagnosis of rheumatoid arthritis (RA) based on the American College of Rheumatology Criteria 1987 Participants must have been on Methotrexate (MTX) for 12 weeks at the stable dose for at least 4 weeks Participants using oral corticosteroids, must have been on a stable dose of prednisone less than 10 milligram per day (mg/day) or its equivalent for at least 4 weeks before screening or if currently not using corticosteroids, the participant must not have received corticosteroids for at least 4 weeks before screening Participants with moderate to severe RA (Disease Activity Score [DAS28] greater than 3.2) Male participants shall adopt contraceptive measures during the trial and within 6 months after the completion of trial (such as spermicidal barrier), or their female sexual partners shall agree to adopt effective contraceptive measures during the trial or within 6 months after the completion of trial (such as oral contraceptives, contraceptives for injection, intrauterine device [IUD], or sterilization by surgery); female participants of childbearing potential with negative urine pregnancy test upon enrollment in addition to adopting the said contraceptive measures Exclusion Criteria: Participant who has a known allergy to human immunoglobulin proteins or other components of infliximab Participant who has a history of receiving infliximab or any other biological preparations Participant who is in stage IV RA evaluated by X-ray Participants suffering from tuberculosis Female participant or male participant's wife who plans to become pregnant during this study and within 6 months after completion of this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infliximab + Methotrexate (Moderate RA)<br>Participants with moderate RA (score greater than 3.2, but less than 5.1 on the disease activity score [DAS] 28) received infliximab 3 milligram per kilogram (mg/kg) intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) at Week 0, 2, 6, 14 and 22 along with oral MTX IN a stable dose of 7.5 to 20 mg per week (equal to the dose used before participation in the study) for 22 weeks. | Drug: Infliximab<br>* Infliximab 3 mg per kg intravenous infusion at Week 0, 2, 6, 14 and 22.<br>Drug: Methotrexate<br>* MTX stable dose (7.5 to 20 mg/week equal to the dose used before participation in the study) for 22 weeks.<br>|
| Experimental: Infliximab + Methotrexate (Severe RA)<br>Participants with severe RA (score greater than 5.1 on the DAS 28) received infliximab 3 mg/kg intravenous infusion at Week 0, 2, 6, 14 and 22 along with oral MTX in a stable dose of 7.5 to 20 mg per week (mg/week) equal to the dose used before participation in the study) for 22 weeks. | Drug: Infliximab<br>* Infliximab 3 mg per kg intravenous infusion at Week 0, 2, 6, 14 and 22.<br>Drug: Methotrexate<br>* MTX stable dose (7.5 to 20 mg/week equal to the dose used before participation in the study) for 22 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving American College of Rheumatology Score 20 Percent (ACR20) Response | ACR20 is achieved if the participant has 20% improvement from Baseline in swollen joint count; tender joint count and in at least 3 of the following 5 assessments: participants' assessment of pain; participants' global assessment of disease activity; physician's global assessment of disease activity; participants' assessment of physical function (Health Assessment Questionnaire [HAQ]) and C-reactive protein (CRP). | Week 26 | 
| Percentage of Participants Achieving American College of Rheumatology Score 50 Percent (ACR50) Response | ACR50 is achieved if the participant has 50% improvement from Baseline in swollen joint count; tender joint count and in at least 3 of the following 5 assessments: participants' assessment of pain; participants' global assessment of disease activity; physician's global assessment of disease activity; participants' assessment of physical function (Health Assessment Questionnaire [HAQ]) and C-reactive protein (CRP). | Week 26 | 
| Percentage of Participants Achieving American College of Rheumatology Score 70 Percent (ACR70) Response | ACR70 is achieved if the participant has 70% improvement from Baseline in swollen joint count; tender joint count and in at least 3 of the following 5 assessments: participants' assessment of pain; participants' global assessment of disease activity; physician's global assessment of disease activity; participants' assessment of physical function (Health Assessment Questionnaire [HAQ]) and C-reactive protein (CRP). | Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Swollen Joints Count at Week 26 | Number of swollen joints were determined by examination of 28 joints and identifying when swelling is present. The number of swollen joints was recorded on the joint assessment form at each visit; the swelling was graded on a scale ranging from 0-2 (0=no swelling, 1=swelling, but bony landmarks seen, 2=swelling but bone marks not seen). Participants categorized as Hepatitis B Virus antigen (HBsAb) positive/negative (at least 1 of HbsAg, HBeAg, Anti-HbeAg and Anti-HbcAg were positive or all were negative). | Baseline and Week 26 | 
| Change From Baseline in Tender Joints Count at Week 26 | Number of tender joints was determined by examination of 28 joints and identifying when tenderness is present. The number of tender joints was recorded on the joint assessment form at each visit; the tenderness of symptomatic joints was graded on a scale ranging from 0-3 (0=no pain, 1=mild, 2= moderate and 3=severe). | Baseline and Week 26 | 
| Change From Baseline in Participant's Pain Visual Analogue Scale (VAS) Score at Week 26 | Participant's pain was assessed on VAS of 0 to 100 mm (0=not at all to 100=extreme pain). | Baseline and Week 26 | 
| Change From Baseline in Participants' Global Disease Assessment at Week 26 | Participants scored the overall disease state using VAS of 0-100 mm. Participants might have assessed the Control of their current disease using 0 mm=very good to 100 mm=very poor scale. | Baseline and Week 26 | 
| Change From Baseline in Physicians' Global Disease Assessment at Week 26 | Physicians scored the overall disease state using VAS of 0-100 mm. Physicians might have assessed the activity of RA using 0=no active RA to 100=most serious active RA scale. | Baseline and Week 26 | 
| Change From Baseline in Duration of Morning Stiffness at Week 26 | Duration of morning stiffness: Time elapsed in minutes when participant woke up in morning and was able to resume normal activities without stiffness. Increase in stiffness duration from Baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement. | Baseline and Week 26 | 
| Change From Baseline in Health Assessment Questionnaire (HAQ) at Week 26 | The HAQ, a 20-question instrument, assesses the degree of difficulty a person has in accomplishing tasks in eight functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores). Responses in each area are scored from 0=no difficulty to 3=inability to perform a task in that area. | Baseline and Week 26 | 
| Change From Baseline in C-Reactive Protein (CRP) at Week 26 | CRP is a protein found in the blood, the levels of which rise in response to inflammation. | Baseline and Week 26 | 
| Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 26 | ESR is also called a sedimentation rate or Westergren ESR, is the rate at which red blood cells sediment in a period of 1 hour. It is a common hematology test, and is a non-specific measure of inflammation. | Baseline and Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arthritis, Rheumatoid, Infliximab, Methotrexate