Clinical trial NCT00796705: 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
Overall status: TERMINATED
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2008-11-24
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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:

  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

Primary outcomes:
measure: Change in the Disease Activity Score Using C-reactive Protein (DAS28[CRP]) From Baseline to Week 12 in Non-Switchers Versus Switchers.
timeFrame: Baseline, Week 12
measure: Change in the Disease Activity Score Using C-reactive Protein (DAS28[CRP]) From Baseline to Week 12.
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Participants With a Disease Activity Score Using C-reactive Protein (DAS28[CRP]) Value <= 3.2 (Low Disease Activity) at Week 12
timeFrame: Week 12
measure: Participants With a Disease Activity Score Using C-reactive Protein (DAS28[CRP]) Value < 2.6 (Remission) at Week 12
timeFrame: Week 12
measure: 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)
timeFrame: Baseline, Week 12
measure: Participants With an ACR 20 Response at Week 12
timeFrame: Week 12
measure: Participants With an ACR 50 Response at Week 12
timeFrame: Week 12
measure: Participants With an ACR 70 Response at Week 12
timeFrame: Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Sarasota
country: United States
facility: Sarasota Arthritis Research Center
state: Florida
city: Tampa
country: United States
facility: Tampa Medical Group
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Lansing
country: United States
facility: Justus Fiechtner, MD, PC
state: Michigan
city: Manhassett
country: United States
facility: Feinstein Institute for Medical Research NS-LIJ
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Charlotte
country: United States
facility: Carolina Bone and Joint
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Pittsburgh
name: Larry Moreland, MD
role: STUDY_CHAIR
affiliation: Stanford University
name: Mark Genovese, MD
role: STUDY_CHAIR
References:
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.
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.
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.