Switching Anti-TNF-Alpha Agents in Rheumatoid Arthritis (RA)

NCT00796705 | Terminated Phase 4 Results DMC

• 1 other identifier: DAIT ARA05
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 16

Brief Summary

Rheumatoid Arthritis (RA) is a systemic inflammatory autoimmune disorder that leads to inflammation and progressive joint damage affecting 2.5 million people in the United States. The primary purpose of this study is to determine the effectiveness of switching to an alternative Tumor Necrosis Factor (TNF) alpha inhibitor in comparison to continuing treatment with an existing TNF-alpha inhibitor in adults suffering from RA in a setting of inadequate clinical response to etanercept or adalimumab.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• Change in the Disease Activity Score Using C-reactive Protein (DAS28[CRP]) From Baseline to Week 12 in Non-Switchers Versus Switchers.

  The DAS28 is a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (\>5.1=high disease activity; \<=3.2=low disease activity; \<2.6=remission); a continuous variable which is a composite of 4 variables(the number of tender joints out of 28, the number of swollen joints out of 28 joints, serum C-reactive protein in mg/L (CRP) and subject assessment of disease activity measure on a visual analogue scale (VAS) of 100 mm).

  Baseline, Week 12

• Change in the Disease Activity Score Using C-reactive Protein (DAS28[CRP]) From Baseline to Week 12.

  The DAS28 is a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (\>5.1=high disease activity; \<=3.2=low disease activity; \<2.6=remission); a continuous variable which is a composite of 4 variables(the number of tender joints out of 28, the number of swollen joints out of 28 joints, serum C-reactive protein in mg/L (CRP) and subject assessment of disease activity measure on a visual analogue scale (VAS) of 100 mm).

  Baseline, Week 12

Secondary Outcomes (6)

• Participants With a Disease Activity Score Using C-reactive Protein (DAS28[CRP]) Value <= 3.2 (Low Disease Activity) at Week 12

  Week 12

• Participants With a Disease Activity Score Using C-reactive Protein (DAS28[CRP]) Value < 2.6 (Remission) at Week 12

  Week 12

• Participants With a Decrease in Disease Activity Score Using C-reactive Protein (DAS28[CRP]) Value of >1.2 From Baseline to Week 12 (European League Against Rheumatism (EULAR) Definition of a Moderate Response)

  Baseline, Week 12

• Participants With an ACR 20 Response at Week 12

  Week 12

• Participants With an ACR 50 Response at Week 12

  Week 12

Study Arms (2)

Adalimumab / Adalimumab Placebo

EXPERIMENTAL

1 sub-cutaneous (SQ) injection of adalimumab or 1 SQ injection of placebo will be given in a blinded and alternating fashion for a total of 12 weeks

Drug: Adalimumab; Drug: Adalimumab placebo

Etanercept

EXPERIMENTAL

Participants will receive 1 SQ injection of etanercept each week for 12 weeks

Drug: Etanercept

Interventions

Adalimumab DRUG

40 mg injection of adalimumab administered subcutaneously

Also known as: Humira

Adalimumab / Adalimumab Placebo

Adalimumab placebo DRUG

1.0 ml .9% saline placebo administered subcutaneously

Also known as: Humira placebo

Adalimumab / Adalimumab Placebo

Etanercept DRUG

50 mg dimeric fusion protein administered subcutaneously

Also known as: Enbrel

Etanercept

Eligibility Criteria

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

You may qualify if:

• Diagnosis of Rheumatoid Arthritis
• Current treatment with either etanercept or adalimumab for at least 12 weeks prior to randomization
• Disease Activity Score (DAS) C-reactive Protein (CRP) 28 ≥ 4.4
• Treatment with concomitant Disease-Modifying Anti-Rheumatic Drugs (DMARDs) is permitted but not required as described below:
• Methotrexate - maximum dose of 25 mg per os (PO), intra-muscular (IM), or SQ weekly.
• Leflunomide - maximum dose of 20 mg PO daily.
• Sulfasalazine - maximum dose of 1,500 mg PO twice daily.
• Hydroxychloroquine - maximum dose of 400 mg PO daily.
• If taking DMARD(s), subjects must be on stable doses for at least 12 weeks prior to randomization.
• If treated with prednisone (or equivalent corticosteroid), on a stable dose of \<= 10 mg/day for 28 days prior to randomization.
• Agree to use appropriate form of contraception. More information on this criterion can be found in the protocol.

You may not qualify if:

• Diagnosis of another autoimmune disease likely to require immunosuppression. More information on this criterion can be found in the protocol.
• Failing treatment with etanercept if previously treated with adalimumab
• Failing treatment with adalimumab if previously treated with etanercept
• Intraarticular injection within 4 weeks prior to randomization
• Concurrent use of any biologic agent other than etanercept or adalimumab
• Concomitant immunosuppressive therapy other than the Disease-Modifying Anti-Rheumatic Drugs (DMARDs), non-steroidal anti-inflammatory drugs (NSAIDs), or corticosteroids specified in the protocol
• Presence of open leg ulcers
• Chronic or persistent infection that may be worsened by immunosuppressive treatment. More information on this criterion can be found in the protocol.
• Active infection or severe infections requiring hospitalization or treatment with intravenous antibiotics, antivirals, or antifungals within 30 days prior to randomization
• History of positive Purified Protein Derivative (PPD) or chest x-ray findings indicative of prior tuberculosis infection
• Any medical condition or treatment that, in the opinion of the investigator, would put the subject at risk by participation in the study
• History of malignancy. More information on this criterion can be found in the protocol.
• Certain abnormal laboratory values. More information on this criterion can be found in the protocol.
• Investigational biological or chemical agents within 4 weeks prior to randomization.
• History of drug or alcohol abuse within a year prior to randomization

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (16)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

Sarasota Arthritis Research Center

Sarasota, Florida, 34239, United States

Location

Tampa Medical Group

Tampa, Florida, 33614, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Justus Fiechtner, MD, PC

Lansing, Michigan, 48910, United States

Location

Feinstein Institute for Medical Research NS-LIJ

Manhassett, New York, 14642, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Carolina Bone and Joint

Charlotte, North Carolina, 28210, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

Location

Baylor Research Institute

Dallas, Texas, 75231, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (3)

• Villeneuve E, Haraoui B. To switch or to change class-the biologic dilemma in rheumatoid arthritis. Nat Rev Rheumatol. 2010 May;6(5):301-5. doi: 10.1038/nrrheum.2010.45. Epub 2010 Apr 13.

  PMID: 20386564 BACKGROUND

• Rubbert-Roth A, Finckh A. Treatment options in patients with rheumatoid arthritis failing initial TNF inhibitor therapy: a critical review. Arthritis Res Ther. 2009;11 Suppl 1(Suppl 1):S1. doi: 10.1186/ar2666. Epub 2009 Apr 6.

  PMID: 19368701 BACKGROUND

• van Gestel AM, Haagsma CJ, van Riel PL. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum. 1998 Oct;41(10):1845-50. doi: 10.1002/1529-0131(199810)41:103.0.CO;2-K.

  PMID: 9778226 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Adalimumab; Etanercept

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, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Immunoglobulin Constant Regions; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Limitations and Caveats

The study terminated early due to recruitment feasibility issues. Thirteen subjects were enrolled and received treatment. No mechanistic analyses were performed.

Results Point of Contact

• Title: Associate Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Larry Moreland, MD

  University of Pittsburgh

  STUDY CHAIR

• Mark Genovese, MD

  Stanford University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2008
• First Posted: November 24, 2008
• Study Start: November 1, 2008
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: October 4, 2012
• Results First Posted: August 13, 2012

Record last verified: 2012-08

Locations

US (16)