Clinical trial NCT01211678: Biomarkers of Anti-TNF-α Therapy Efficacy in Rheumatoid Arthritis to Define Unresponsive Patients
Official title: Biomarkers of Anti-TNF-α Therapy Efficacy in Rheumatoid Arthritis to Define Unresponsive Patients (BATTER-UP)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Arthritis, Rheumatoid
Lead sponsor: Biogen
Sponsor class: INDUSTRY
Collaborators: name: Crescendo Biosciences
First posted: 2010-09-29
Enrollment: 301
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants who meet American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA) and who, in the opinion of their treating rheumatologist, are not adequately treated with existing therapy and should begin treatment with either an anti TNF agent for the first time or with a different anti-TNF agent.

Brief summary: The primary objective of this study was to validate the ability of an 8-gene biomarker set to differentiate between participants who met or did not meet European League Against Rheumatism (EULAR) Disease Activity Score (DAS)-28 Good Response criteria after treatment with anti-Tumor Necrosis Factor (TNF) therapy for 14 weeks in approximately 200 anti-TNF-naïve participants. The secondary objectives of this study was (i) to compare the behavior of the 8-gene marker set in participants who were anti-TNF naïve versus those who began their second anti-TNF treatment , (ii) to develop, maintain, and utilize a biorepository of serum, plasma, RNA, and deoxyribonucleic acid (DNA) samples for additional experiments and analyses and (iii) to discover novel genetic (DNA) predictors of response to anti-TNF therapy.


Eligibility criteria: Key Inclusion Criteria

To be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of enrollment:

* Are willing and able to provide informed consent..
* Meet the ACR criteria for RA as determined by a rheumatologist who is board certified in Rheumatology or a member of the ACR.
* Have 4 or more tender and 4 or more swollen joints out of 28 joints as assessed by their treating rheumatologist or a trained joint assessor.
* Subjects are not taking any of the following treatments and/or have washed out for the minimum duration as defined below. If subjects are currently taking these treatments, must have been on a stable dosing regimen for the minimum duration as defined below:

  * Oral DMARDs (MTX, hydroxychloroquine, sulfasalazine, leflunomide, cyclosporine, azathioprine): on drug for at least 3 months and washed out or stable for at least 6 weeks prior to baseline sample collection.
  * Oral corticosteroids: washed out or stable AND ≤10 mg/day of prednisone equivalent for at least 4 weeks prior to baseline sample collection.
  * Intraarticular or parenteral corticosteroids: Washed out or stable for at least 4 weeks prior to baseline sample collection.
  * NSAIDs: Washed out or stable for at least 2 weeks prior to baseline sample collection.
* Are about to start treatment with an anti-TNF agent approved for the treatment of RA for the first time OR Have not, in the opinion of the treating rheumatologist, achieved or maintained an adequate response to treatment with their first anti-TNF agent (any anti-TNF agent approved for the treatment of RA), and have been prescribed a different anti TNF agent. Subjects who switch for any reason other than lack of efficacy will be excluded.

Key Exclusion Criteria

Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of enrollment:

* Any medical condition that would preclude safe use of an anti-TNF agent for at least 14 weeks.
* Previous participation in the present study as a subject in the anti-TNF-naïve group.
* Prior exposure to 2 or more anti-TNF agents.
* Prior exposure to Orencia (abatacept, or CTLA4-Ig) and/or Rituxan (anti CD20), or other biologic therapy for RA or other diseases.

Note: Other protocol defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Validation of the ability of an 8-gene biomarker set to differentiate between participants who meet or do not meet EULAR DAS-28 Good response criteria after treatment with anti-TNF therapy
timeFrame: 14 weeks
Secondary outcomes:
measure: Comparison of the behavior of the 8-gene marker set in participants who are anti-TNF naïve versus those who begin their second anti-TNF treatment
timeFrame: 14 weeks
measure: Development, maintenance, and utilization of a biorepository of serum, plasma, RNA, and deoxyribonucleic acid (DNA) samples for additional experiments and analyses.
timeFrame: 14 weeks
measure: Discovery of novel genetic (DNA) predictors of response to anti-TNF therapy.
timeFrame: 14 weeks
Other outcomes:
Locations:
city: Murietta
country: United States
facility: Research Site
state: California
city: Longmont
country: United States
facility: Research Site
state: Colorado
city: Lewes
country: United States
facility: Research Site
state: Delaware
city: Dunedin
country: United States
facility: Research Site
state: Florida
city: Ocala
country: United States
facility: Research Site
state: Florida
city: Orange Park
country: United States
facility: Research Site
state: Florida
city: Morton Grove
country: United States
facility: Research Site
state: Illinois
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Plymouth
country: United States
facility: Research Site
state: Massachusetts
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Reno
country: United States
facility: Research Site
state: Nevada
city: Berkeley Heights
country: United States
facility: Research Site
state: New Jersey
city: Summit
country: United States
facility: Research Site
state: New Jersey
city: Floral Park
country: United States
facility: Research Site
state: New York
city: Orchard Park
country: United States
facility: Research Site
state: New York
city: Smithtown
country: United States
facility: Research Site
state: New York
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Wilmington
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Mayfield Village
country: United States
facility: Research Site
state: Ohio
city: Middleburg Heights
country: United States
facility: Research Site
state: Ohio
city: Edmund
country: United States
facility: Research Site
state: Oklahoma
city: Duncansville
country: United States
facility: Research Site
state: Pennsylvania
city: Mrytle Beach
country: United States
facility: Research Site
state: South Carolina
city: Dallas
country: United States
facility: Research Site
state: Texas
city: San Anotnio
country: United States
facility: Research Site
state: Texas
city: Burke
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Spokane
country: United States
facility: Research Site
state: Washington
city: Franklin
country: United States
facility: Research Site
state: Wisconsin
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: