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

This study has been terminated.
(Lack of Enrollment)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00796705
First received: November 20, 2008
Last updated: September 28, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Adalimumab
Drug: Adalimumab placebo
Drug: Etanercept
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Switching Anti-TNF-alpha Agents in Patients With RA With An Inadequate Response to TNF-alpha Inhibition

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Change in the Disease Activity Score Using C-reactive Protein (DAS28[CRP]) From Baseline to Week 12 in Non-Switchers Versus Switchers. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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).

  • Change in the Disease Activity Score Using C-reactive Protein (DAS28[CRP]) From Baseline to Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Participants With a Disease Activity Score Using C-reactive Protein (DAS28[CRP]) Value <= 3.2 (Low Disease Activity) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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).

  • Participants With a Disease Activity Score Using C-reactive Protein (DAS28[CRP]) Value < 2.6 (Remission) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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).

  • 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) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    The EULAR definition of a Moderate Response is a decrease from baseline in the DAS28[CRP] value of ≥ 1.2.

  • Participants With an ACR 20 Response at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    The American College of Rheumatology (ACR) 20 Responder Index is defined as someone who achieved at least 20% improvement in the tender and swollen 28-joint count, and 20% improvement in at least three of the following 5 measures:

    • Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm)
    • Patient's global assessment of disease activity (VAS 100 mm)
    • Physician's global assessment of disease activity (VAS 100 mm)
    • Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score)
    • Acute phase reactant (CRP)

  • Participants With an ACR 50 Response at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    The American College of Rheumatology (ACR) 50 Responder Index is defined as someone who achieved at least 50% improvement in the tender and swollen 28-joint count, and 50% improvement in at least three of the following 5 measures:

    • Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm)
    • Patient's global assessment of disease activity (VAS 100 mm)
    • Physician's global assessment of disease activity (VAS 100 mm)
    • Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score)
    • Acute phase reactant (CRP)

  • Participants With an ACR 70 Response at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    The American College of Rheumatology (ACR) 70 Responder Index is defined as someone who achieved at least 70% improvement in the tender and swollen 28- joint count, and 70% improvement in at least three of the following the following 5 measures:

    • Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm)
    • Patient's global assessment of disease activity (VAS 100 mm)
    • Physician's global assessment of disease activity (VAS 100 mm)
    • Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score)
    • Acute phase reactant (CRP)


Enrollment: 13
Study Start Date: November 2008
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adalimumab / Adalimumab Placebo
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
40 mg injection of adalimumab administered subcutaneously
Other Name: Humira
Drug: Adalimumab placebo
1.0 ml .9% saline placebo administered subcutaneously
Other Name: Humira placebo
Experimental: Etanercept
Participants will receive 1 SQ injection of etanercept each week for 12 weeks
Drug: Etanercept
50 mg dimeric fusion protein administered subcutaneously
Other Name: Enbrel

Detailed Description:

Over the past 10 years, advancements in biotechnology have revolutionized Rheumatoid Arthritis (RA) therapeutics with biologically-derived immunomodulating compounds. Tumor Necrosis Factor (TNF) alpha inhibitors constitute the largest class of these new biologic therapies. The purpose of this study is to determine the effectiveness of switching to an alternative TNF-alpha inhibitor in comparison to continuing treatment with an existing TNF-alpha inhibitor in adults suffering from RA who have had inadequate clinical response to the study drugs etanercept and adalimumab.

This study will last approximately 16 weeks. Participants will be randomized into two arms and receive injections once per week for 12 weeks. Participants in the adalimumab arm will receive alternating subcutaneous adalimumab and adalimumab placebo injections. Participants in the etanercept arm will receive subcutaneous etanercept injections.

This study consists of thirteen study visits after randomization. Study visits will occur on a weekly basis for 12 weeks prior to a follow-up visit at Week 16. A vital signs measurement and adverse event assessment will occur at each visit. A physical exam, assessment of tender and swollen joints, medication assessment, and blood collection will occur at Weeks 4, 8, 12, and 16.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:

    1. Methotrexate - maximum dose of 25 mg per os (PO), intra-muscular (IM), or SQ weekly.
    2. Leflunomide - maximum dose of 20 mg PO daily.
    3. Sulfasalazine - maximum dose of 1,500 mg PO twice daily.
    4. 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.

Exclusion Criteria:

  • 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
  • Concomitant use of DMARDs other than those described in Inclusion Criteria within 12 weeks of 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
  • Treatment with natalizumab, rituximab, or another B-cell depleting therapy within a year prior to randomization
  • Treatment with infliximab, abatacept, tocilizumab, golimumab, or certolizumab pegol within 12 weeks prior to randomization.
  • Known allergy or hypersensitivity to study products
  • Any psychiatric disorder that prevents the participant from providing informed consent
  • Inability to follow protocol instructions
  • Pregnant or breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00796705

Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294
United States, California
Stanford University
Palo Alto, California, United States, 94304
United States, Connecticut
Yale New Haven Hospital
New Haven, Connecticut, United States, 06520
United States, Florida
Sarasota Arthritis Research Center
Sarasota, Florida, United States, 34239
Tampa Medical Group
Tampa, Florida, United States, 33614
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Michigan
Justus Fiechtner, MD, PC
Lansing, Michigan, United States, 48910
United States, New York
Feinstein Institute for Medical Research NS-LIJ
Manhassett, New York, United States, 14642
University of Rochester
Rochester, New York, United States, 14642
United States, North Carolina
Carolina Bone and Joint
Charlotte, North Carolina, United States, 28210
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Oklahoma
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States, 16635
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15260
United States, Texas
Baylor Research Institute
Dallas, Texas, United States, 75231
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Investigators
Study Chair: Larry Moreland, MD University of Pittsburgh
Study Chair: Mark Genovese, MD Stanford University
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00796705     History of Changes
Other Study ID Numbers: DAIT ARA05
Study First Received: November 20, 2008
Results First Received: July 5, 2012
Last Updated: September 28, 2012
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Adalimumab
TNFR-Fc fusion protein
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Central Nervous System Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014