Official Title: “Induction of Remission in RA Patients at Low Disease Activity by Additional Infliximab-Therapy”

This Phase 3, randomized, open-label, multicenter study in rheumatoid arthritis (RA) patients with low disease activity (DAS 28 >2.8 and <3.5) is being conducted to evaluate induction of remission by adding infliximab to pre-existing treatment versus no additional treatment. All subjects eligible for this study, aged >35 to <=65 years, will have a diagnosis of RA according to ACR criteria, and will be offered additional treatment with infliximab. Prior to the start of treatment, subjects must be on a stable regimen of disease modifying antirheumatic drugs (DMARDs) for at least 3 months. Subjects will be randomized (1:1) to basic therapy with or without infliximab for a total duration of 38 weeks followed by a follow-up period of up to 6 months. Subjects randomized to basic therapy + infliximab will receive infliximab 3 mg/kg at Weeks 0, 2, 6, 14, 22, 30, and 38. The primary objective of the study is to assess the rate of remission according to DAS 28 (<2.6) at the end of treatment (after 38 weeks). Safety assessments include the incidence of adverse events, serious adverse events, and clinically notable abnormal vital signs and laboratory values.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: September 2010

Intervention(s) in this Clinical Trial

• Biological: infliximab
  • infliximab 3 mg/kg and basic treatment
• Drug: DMARDs (methotrexate; chloroquine; leflunomidum; cyclosporin A; sulfasalazine; OM 89.
  • Methotrexate (15 - 25 mg/week); chloroquine; leflunomidum; cyclosporin A; sulfasalazine; OM 89

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Experimental
  • 3 mg/kg infliximab plus basic treatment
• Active Comparator: Basic treatment (DMARDs)
  • Rheumatoid Arthritis basic therapy (DMARDs)

Primary Measures

• Rate of remissions according to DAS 28 (< 2.6)
  • Time Frame: after 38 weeks
    Safety Issue?: No

Secondary Measures

• DAS 28 at Baseline vs at Week 38; Quality of Life; ACR Respone Disease progression (X-ray); Effect of inflammatory markers on response and disease progression; Assess SDAI.
  • Time Frame: Weeks 14, 38, and 62
    Safety Issue?: No

Inclusion Criteria:

• Patients aged >35 and <=65 years with a diagnosis of RA according to ACR criteria for at least 1 year and no more than 10 years prior to start of therapy; have active disease (DAS 28 >2.8 and <3.5), with changes in the DAS 28 score <0.6 within the 6 weeks before inclusion; have stable RA basic therapy according to standard criteria for at least 3 months; have a chest X-ray within 1 month prior to first infusion with no evidence of malignancy, infections, or fibrosis; and have screening laboratory test results that meet prespecified criteria. Patient must have at least one swollen joint.
• Patient must have evidence of erosive disease by x-ray at baseline.

Exclusion Criteria:

• Patients were excluded if they met any of the following criteria:
• Women who are pregnant, nursing, or planning pregnancy within 15 months after screening (i.e., approximately 6 months following last infusion);
• Use of any investigational drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer;
• History of any other therapeutic agent targeted at reducing TNF;
• History of previous administration of infliximab;
• History of receiving human/murine recombinant products or has a known allergy to murine products;
• Serious infection (such as hepatitis, pneumonia or pyelonephritis) in the previous 3 months. Less serious infections (such as acute upper respiratory tract infection [colds] or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator.
• Active TB or evidence of latent TB (positive purified protein derivative [PPD] skin test, a history of old or latent TB or chest X-ray without adequate therapy for TB initiated prior to first infusion of study drug), or evidence of an old or latent TB infection without documented adequate therapy. Patients with a current close contact with an individual with active TB and patients who have completed treatment for active TB within the previous 2 years are explicitly excluded from the trial. Patients with a household member who has a history of active pulmonary
• TB should have had a thorough evaluation for TB prior to study enrollment as recommended by a local infectious disease specialist or published local guidelines of TB control agencies.
• HBs antigen or HCV antibody positive; documented HIV infection;
• Have an opportunistic infection, including but not limited to evidence of active cytomegalovirus, active pneumocystis carinii, aspergillosis, or atypical mycobacterium infection, etc, within the previous 6 months;
• Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, psychiatric, neurologic, or cerebral disease (including demyelinating diseases such as multiple sclerosis);
• Concomitant congestive heart failure >= NYHA II;
• Have a transplanted organ (with the exception of a corneal transplant >3 months prior to screening);
• Fibromyalgia;
• Malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence);
• History of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or peri-aortic areas), or splenomegaly; or
• Known recent substance abuse (drug or alcohol).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 19 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Schering-Plough

Overall Clinical Trial Officials and Contacts

Burkhard F. Leeb, MD Principal Investigator Lower Austrian Center for Rheumatology; Landesklinikum Weinviertel-Stockerau; Director of the Karl Landersteiner Institute  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00521924

Study ID Number: P04644

ClinicalTrials.gov Identifier: NCT00521924

Health Authority: Austria: AGES