Induction of Remission in RA Patients at Low Disease Activity by Additional Infliximab-therapy
Overview
- Phase
- Phase 3
- Intervention
- infliximab
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 8
- Primary Endpoint
- Number of Patients in Remission According to Disease Activity Score (DAS) 28 (< 2.6)
- Status
- Terminated
- Last Updated
- 9 years ago
Overview
Brief 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.
Investigators
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;
Arms & Interventions
Infliximab + basic treatment
3 mg/kg infliximab plus basic treatment
Intervention: infliximab
Basic treatment (DMARDs)
Rheumatoid Arthritis basic therapy (disease modifying anti-rheumatic drugs \[DMARDs\])
Intervention: DMARDs (methotrexate; chloroquine; leflunomidum; cyclosporin A; sulfasalazine; OM 89.
Outcomes
Primary Outcomes
Number of Patients in Remission According to Disease Activity Score (DAS) 28 (< 2.6)
Time Frame: after 38 weeks
The DAS 28 is an assessment of disease activity based on swollen joint count, erythrocyte sedimentation rate, and general health. Patients can be scored on a range of 0 to 10, with lower scores indicating less disease activity.
Secondary Outcomes
- DAS 28 at Baseline vs at Week 38; Quality of Life; American College of Rheumatology (ACR) Response Disease Progression (X-ray); Effect of Inflammatory Markers on Response and Disease Progression; Assess Simplified Disease Activity Index (SDAI).(Weeks 14, 38, and 62)