Back to resultsSwitching Anti-TNF-Alpha Agents in Rheumatoid Arthritis (RA)
Primary Purpose
Rheumatoid Arthritis
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Adalimumab
Adalimumab placebo
Etanercept
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility 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:
- 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.
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
Sites / Locations
- University of Alabama
- Stanford University
- Yale New Haven Hospital
- Sarasota Arthritis Research Center
- Tampa Medical Group
- University of Chicago Medical Center
- Justus Fiechtner, MD, PC
- Feinstein Institute for Medical Research NS-LIJ
- University of Rochester
- Carolina Bone and Joint
- Duke University Medical Center
- Oklahoma Medical Research Foundation
- Altoona Center for Clinical Research
- University of Pittsburgh
- Baylor Research Institute
- University of Utah
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Adalimumab / Adalimumab Placebo
Etanercept
Arm Description
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
Participants will receive 1 SQ injection of etanercept each week for 12 weeks
Outcomes
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.
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.
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
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
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)
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
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
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
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)
Full Information
NCT ID
NCT00796705
First Posted
November 20, 2008
Last Updated
September 28, 2012
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
1. Study Identification
Unique Protocol Identification Number
NCT00796705
Brief Title
Switching Anti-TNF-Alpha Agents in Rheumatoid Arthritis (RA)
Official Title
Switching Anti-TNF-alpha Agents in Patients With RA With An Inadequate Response to TNF-alpha Inhibition
Study Type
Interventional
2. Study Status
Record Verification Date
August 2012
Overall Recruitment Status
Terminated
Why Stopped
Lack of Enrollment
Study Start Date
November 2008 (undefined)
Primary Completion Date
October 2010 (Actual)
Study Completion Date
October 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Adalimumab / Adalimumab Placebo
Arm Type
Experimental
Arm Description
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
Arm Title
Etanercept
Arm Type
Experimental
Arm Description
Participants will receive 1 SQ injection of etanercept each week for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Adalimumab
Other Intervention Name(s)
Humira
Intervention Description
40 mg injection of adalimumab administered subcutaneously
Intervention Type
Drug
Intervention Name(s)
Adalimumab placebo
Other Intervention Name(s)
Humira placebo
Intervention Description
1.0 ml .9% saline placebo administered subcutaneously
Intervention Type
Drug
Intervention Name(s)
Etanercept
Other Intervention Name(s)
Enbrel
Intervention Description
50 mg dimeric fusion protein administered subcutaneously
Primary Outcome Measure Information:
Title
Change in the Disease Activity Score Using C-reactive Protein (DAS28[CRP]) From Baseline to Week 12 in Non-Switchers Versus Switchers.
Description
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).
Time Frame
Baseline, Week 12
Title
Change in the Disease Activity Score Using C-reactive Protein (DAS28[CRP]) From Baseline to Week 12.
Description
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).
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Participants With a Disease Activity Score Using C-reactive Protein (DAS28[CRP]) Value <= 3.2 (Low Disease Activity) at Week 12
Description
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).
Time Frame
Week 12
Title
Participants With a Disease Activity Score Using C-reactive Protein (DAS28[CRP]) Value < 2.6 (Remission) at Week 12
Description
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).
Time Frame
Week 12
Title
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)
Description
The EULAR definition of a Moderate Response is a decrease from baseline in the DAS28[CRP] value of ≥ 1.2.
Time Frame
Baseline, Week 12
Title
Participants With an ACR 20 Response at Week 12
Description
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)
Time Frame
Week 12
Title
Participants With an ACR 50 Response at Week 12
Description
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)
Time Frame
Week 12
Title
Participants With an ACR 70 Response at Week 12
Description
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)
Time Frame
Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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:
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.
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Larry Moreland, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Mark Genovese, MD
Organizational Affiliation
Stanford University
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Yale New Haven Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Sarasota Arthritis Research Center
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34239
Country
United States
Facility Name
Tampa Medical Group
City
Tampa
State/Province
Florida
ZIP/Postal Code
33614
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Justus Fiechtner, MD, PC
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48910
Country
United States
Facility Name
Feinstein Institute for Medical Research NS-LIJ
City
Manhassett
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Carolina Bone and Joint
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28210
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Oklahoma Medical Research Foundation
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Altoona Center for Clinical Research
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15260
Country
United States
Facility Name
Baylor Research Institute
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
20386564
Citation
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.
Results Reference
background
PubMed Identifier
19368701
Citation
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.
Results Reference
background
PubMed Identifier
9778226
Citation
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.
Results Reference
background
Learn more about this trial
Switching Anti-TNF-Alpha Agents in Rheumatoid Arthritis (RA)
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