Induction of Remission in RA Patients at Low Disease Activity by Additional Infliximab Therapy (Study P04644AM1) (TERMINATED)
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: infliximab; DMARDs (methotrexate; chloroquine; leflunomidum; cyclosporin A; sulfasalazine; OM 89.
Intervention description: infliximab 3 mg/kg and basic treatment; Methotrexate (15 - 25 mg/week); chloroquine; leflunomidum; cyclosporin A; sulfasalazine; OM 89
Intervention MeSH terms: Cyclosporine; Chloroquine; Sulfasalazine; Infliximab; Methotrexate; Antirheumatic Agents; Cyclosporins
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 19 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This Phase 3, randomized, open-label, multicenter study in rheumatoid arthritis (RA) patients
      with low disease activity (Disease Activity Score 28 [DAS28] >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 American College of Rheumatology (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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients aged >35 and <=65 years with a diagnosis of rheumatoid arthritis (RA)
             according to American College of Rheumatology (ACR) criteria for at least 1 year and
             no more than 10 years prior to start of therapy; have active disease (Disease Activity
             Score [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 tumor necrosis factor
                  (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 tuberculosis (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.

               -  Hepatitis B surface antigen or Hepatitis C (HCV) antibody positive; documented
                  Human Immunodeficiency Virus (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 >= New York Heart Association (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).