Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00796705
Recruitment Status : Terminated (Lack of Enrollment)
First Posted : November 24, 2008
Results First Posted : August 13, 2012
Last Update Posted : October 4, 2012
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE November 20, 2008
First Posted Date  ICMJE November 24, 2008
Results First Submitted Date  ICMJE July 5, 2012
Results First Posted Date  ICMJE August 13, 2012
Last Update Posted Date October 4, 2012
Study Start Date  ICMJE November 2008
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 17, 2012)
  • 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 ]
    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 ]
    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).
Original Primary Outcome Measures  ICMJE
 (submitted: November 20, 2008)
  • Change in DAS(CRP)28 score [ Time Frame: Through Week 12 ]
  • Change in plasma concentration levels of cytokines [ Time Frame: Through Week 12 ]
  • Change in plasma concentration levels of autoantibodies [ Time Frame: Through Week 12 ]
  • Development of anti-drug antibodies [ Time Frame: Throughout study ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 17, 2012)
  • 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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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)
Original Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2008)
  • ACR 20, ACR 50, ACR 70, and ACR-N responses [ Time Frame: Through Week 12 ]
  • Frequency of adverse events [ Time Frame: Throughout study ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Switching Anti-TNF-Alpha Agents in Rheumatoid Arthritis (RA)
Official Title  ICMJE Switching Anti-TNF-alpha Agents in Patients With RA With An Inadequate Response to TNF-alpha Inhibition
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • 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
  • Drug: Etanercept
    50 mg dimeric fusion protein administered subcutaneously
    Other Name: Enbrel
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: Adalimumab
    • Drug: Adalimumab placebo
  • Experimental: Etanercept
    Participants will receive 1 SQ injection of etanercept each week for 12 weeks
    Intervention: Drug: Etanercept
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 5, 2012)
13
Original Estimated Enrollment  ICMJE
 (submitted: November 20, 2008)
144
Actual Study Completion Date  ICMJE October 2010
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00796705
Other Study ID Numbers  ICMJE DAIT ARA05
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Larry Moreland, MD University of Pittsburgh
Study Chair: Mark Genovese, MD Stanford University
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP