Induction of Remission in RA Patients at Low Disease Activity by Additional Infliximab Therapy (Study P04644AM1) (TERMINATED)

NCT00521924 | Terminated Phase 3 Results

• 2 other identifiers: P046442005-004530-40
• Study Type: interventional
• Target: 8
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Number of Patients in Remission According to Disease Activity Score (DAS) 28 (< 2.6)

  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.

  after 38 weeks

Secondary Outcomes (1)

• 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

Study Arms (2)

Infliximab + basic treatment

EXPERIMENTAL

3 mg/kg infliximab plus basic treatment

Biological: infliximab

Basic treatment (DMARDs)

ACTIVE COMPARATOR

Rheumatoid Arthritis basic therapy (disease modifying anti-rheumatic drugs \[DMARDs\])

Drug: DMARDs (methotrexate; chloroquine; leflunomidum; cyclosporin A; sulfasalazine; OM 89.

Interventions

infliximab BIOLOGICAL

infliximab 3 mg/kg and basic treatment

Also known as: Basic treatment for RA (DMARDs)

Infliximab + basic treatment

DMARDs (methotrexate; chloroquine; leflunomidum; cyclosporin A; sulfasalazine; OM 89. DRUG

Methotrexate (15 - 25 mg/week); chloroquine; leflunomidum; cyclosporin A; sulfasalazine; OM 89

Basic treatment (DMARDs)

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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;
• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• AESCA Pharma GmbH: collaborator

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Infliximab; Antirheumatic Agents; Methotrexate; Chloroquine; Leflunomide; Cyclosporine; Sulfasalazine; OM 89

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Aminoquinolines; Quinolines; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2007
• First Posted: August 28, 2007
• Study Start: June 1, 2007
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: April 12, 2017
• Results First Posted: June 1, 2009

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will share